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Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis
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作者 Yu-Ming Wang Hong-Wei Tao +5 位作者 Feng-Chan Wang Ping Han Na Liu Guo-Jing Zhao Hai-Bo Hu Xue-Chao Lu 《Traditional Medicine Research》 2024年第2期52-65,共14页
Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disor... Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling. 展开更多
关键词 Mufangji tang pulmonary arterial hypertension APOPTOSIS inflammatory response oxidative stress vascular remodeling
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Hypoxia promotes pulmonary vascular remodeling via HIF-1α to regulate mitochondrial dynamics 被引量:6
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作者 Xi CHEN Jia-Mei YAO +5 位作者 Xia FANG Cui ZHANG Yu-Shu YANG Cheng-Ping HU Qiong CHEN Guang-Wei ZHONG 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2019年第12期855-871,共17页
Background Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension(PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the... Background Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension(PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation and apoptosis balance. However, the molecular mechanism underlying of this balance is still unknown. Methods To clarify the biological effects of hypoxic air exposure and hypoxia-inducible factor-1α(HIF-1α) on pulmonary arterial smooth muscle cell(PASMC) and pulmonary arterial hypertension rats, the cells were cultured in a hypoxic chamber under oxygen concentrations. Cell viability, reactive oxygen species level, cell death, mitochondrial morphology, mitochondrial membrane potential, mitochondrial function and mitochondrial biosynthesis, as well as fission-and fusion-related proteins, were measured under hypoxic conditions. In addition, rats were maintained under hypoxic conditions, and the right ventricular systolic pressure, right ventricular hypertrophy index and right ventricular weight/body weight ratio were examined and recorded. Further, we assessed the role of HIF-1α in the development and progression of PH using HIF-1α gene knockdown using small interfering RNA transfection. Mdivi-1 treatment was performed before hypoxia to inhibit dynamin-related protein 1(Drp1). Results We found that HIF-1α expression was increased during hypoxia, which was crucial for hypoxia-induced mitochondrial dysfunction and hypoxia-stimulated PASMCs proliferation and apoptosis. We also found that targeting mitochondrial fission Drp1 by mitochondrial division inhibitor Mdivi-1 was effective in PH model rats. The results showed that mitochondrial dynamics were involved in the pulmonary vascular remodeling under hypoxia in vivo and in vitro. Furthermore, HIF-1α also modulated mitochondrial dynamics in pulmonary vascular remodeling under hypoxia through directly regulating the expression of Drp1. Conclusions In conclusion, our data suggests that abnormal mitochondrial dynamics could be a marker for the early diagnosis of PH and monitoring disease progression. Further research is needed to study the signaling pathways that govern mitochondrial fission/fusion in PH. 展开更多
关键词 Dynamin-related protein 1 HYPOXIA Hypoxia-inducible factor-1α Mitochondrial dynamics Pulmonary vascular remodeling
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The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension 被引量:5
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作者 甄国华 张珍祥 徐永健 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2003年第4期356-358,368,共4页
We investigated the expression of heme oxygenase 1 (HO 1) gene and production of endogenous carbon monoxide (CO) in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effe... We investigated the expression of heme oxygenase 1 (HO 1) gene and production of endogenous carbon monoxide (CO) in the rat lung tissue at different time points of chronic hypoxic pulmonary hypertension and the effect of hemin on the expression of HO 1 gene and pulmonary hypertension. A rat model of hypoxic pulmonary hypertension was recreated by exposure to intermittent normobaric hypoxic environment (10 % O 2). Reverse transcriptase polymerase chain reaction (RT PCR) was performed to determine the level of HO 1 mRNA in the rat lung tissue and double wave length spectrophotometry was used to evaluate the quantity of COHb in arterial blood. Cardiac catheterization was employed to measure the right ventricular systolic pressure (RVSP) and HE staining was performed in dissected lung tissue to observe the pathological changes of the intra acinar pulmonary arteries (IAPA). It was found that (1) There was a low level of HO 1 mRNA in normal rat lung tissue, but the level of HO 1 mRNA increased by 2-4 times in the lung tissue of hypoxic rats ( P <0.01). The quantity of COHb was 2-3 times those of control group ( P <0.01 or P <0.05). These were accompanied by the increased of RVSP and the thickened IAPA; (2) Hemin could keep the HO 1 mRNA and COHb in the hypoxic rat lung tissue at a high level, and partially suppressed the increase of rat RVSP, thereby ameliorating the pathological changes of IAPA. In conclusion, the upregulation of the expression of HO 1 gene and production of CO in the rat lung of hypoxic pulmonary hypertension plays a role of inhibition in the development of hypoxic pulmonary hypertension. Hemin has a therapeutic effect on hypoxic pulmonary hypertension. 展开更多
关键词 heme oxygenase HYPOXIA pulmonary hypertension pulmonary vascular remodeling
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Effects of low ambient temperatures and dietary vitamin C supplementation on pulmonary vascular remodeling and hypoxic gene expression of 21-d-old broilers 被引量:1
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作者 ZENG Qiu-feng YANG Xia +7 位作者 ZHENG Ping ZHANG Ke-ying LUO Yu-heng DING Xue-mei BAI Shi-ping WANG Jian-ping XUAN Yue SU Zhuo-wei 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2016年第1期183-190,共8页
The objective of this study was to evaluate the effects of low ambient temperature (LAT) and dietary vitamin C (VC) sup- plementation on pulmonary vascular remodeling (PVR) and the relative expression of hypoxia... The objective of this study was to evaluate the effects of low ambient temperature (LAT) and dietary vitamin C (VC) sup- plementation on pulmonary vascular remodeling (PVR) and the relative expression of hypoxia inducible factor-la (HIF-la), vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2) mRNA of lungs in 21-d-old broilers. 400 1-d-old male Cobb broilers were assigned randomly to 4 treatments as follows for 21 d: 1 ) LAT and a basal diet; 2) LAT and a basal diet supplemented with 1 000 mg kg-1 VC (LAT+VC); 3) normal ambient temperature (NAT) and a basal diet; 4) NAT and a basal diet supplemented with 1 000 mg kg-1 VC (NAT+VC). Each treatment was composed of 10 replicates of 10 birds per replicate. Samples of lung were collected after the broilers were killed at d 21. LAT increased the ratio of vessel wall area to vessel total area (WA/TA, %) and mean media thickness in pulmonary arterioles (mMTPA, %) (P〈0.05). Dietary VC supplementation decreased mMTPA (P〈0.05), but had no effect on the WA/TA. LAT increased (P〈0.05) the relative mRNA expression of HIF-la, VEGF and VEGFR-2, while adding VC to the diet could decrease (P〈0.05) their relative mRNA expression. A significant positive correlation existed between the level of VEGF mRNA expression and the value of WA/WT (P〈0.05) or mMTPA (P〈0.05). These results suggested LAT resulted in pulmonary vascular remodeling, and the increase of HIF-la, VEGF and VEGFR-2 mRNA expression, and dietary VC supplementation can alleviate pulmonary vascular remodeling in broiler by affecting these gene expression. 展开更多
关键词 BROILER hypoxia inducible factor-la low ambient temperature pulmonary vascular remodeling vitamin C
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Increasing angiotensin-converting enzyme(ACE)2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest 被引量:1
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作者 Hong-li Xiao Lian-xing Zhao +5 位作者 Jun Yang Nan Tong Le An Guo-xing Wang Miao-rong Xie Chun-sheng Li 《World Journal of Emergency Medicine》 SCIE CAS CSCD 2022年第3期208-214,共7页
BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery re... BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE. 展开更多
关键词 Acute pulmonary embolism Cardiac arrest Early pulmonary vascular remodeling Angiotensin-converting enzyme
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Profilin-1 is involved in macroangiopathy induced by advanced glycation end products via vascular remodeling and inflammation 被引量:1
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作者 Zhi-Lin Xiao Li-Ping Ma +3 位作者 Da-Feng Yang Mei Yang Zhen-Yu Li Mei-Fang Chen 《World Journal of Diabetes》 SCIE 2021年第11期1875-1893,共19页
BACKGROUND The accumulation of advanced glycation end products(AGEs)have been implicated in the development and progression of diabetic vasculopathy.However,the role of profilin-1 as a multifunctional actin-binding pr... BACKGROUND The accumulation of advanced glycation end products(AGEs)have been implicated in the development and progression of diabetic vasculopathy.However,the role of profilin-1 as a multifunctional actin-binding protein in AGEs-induced atherosclerosis(AS)is largely unknown.AIM To explore the potential role of profilin-1 in the pathogenesis of AS induced by AGEs,particularly in relation to the Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)signaling pathway.METHODS Eighty-nine individuals undergoing coronary angiography were enrolled in the study.Plasma cytokine levels were detected using ELISA kits.Rat aortic vascular smooth muscle cells(RASMCs)were incubated with different compounds for different times.Cell proliferation was determined by performing the MTT assay and EdU staining.An AGEs-induced vascular remodeling model was established in rats and histological and immunohistochemical analyses were performed.The mRNA and protein levels were detected using real-time PCR and Western blot analysis,respectively.In vivo,shRNA transfection was performed to verify the role of profilin-1 in AGEs-induced proatherogenic mediator release and aortic remodeling.Statistical analyses were performed using SPSS 22.0 software.RESULTS Compared with the control group,plasma levels of profilin-1 and receptor for AGEs(RAGE)were significantly increased in patients with coronary artery disease,especially in those complicated with diabetes mellitus(P<0.01).The levels of profilin-1 were positively correlated with the levels of RAGE(P<0.01);additionally,the levels of both molecules were positively associated with the degree of coronary artery stenosis(P<0.01).In vivo,tail vein injections of AGEs induced the release of proatherogenic mediators,such as asymmetric dimethylarginine,intercellular adhesion molecule-1,and the N-terminus of procollagen III peptide,concomitant with apparent aortic morphological changes and significantly upregulated expression of the profilin-1 mRNA and protein in the thoracic aorta(P<0.05 or P<0.01).Downregulation of profilin-1 expression with an shRNA significantly attenuated AGEs-induced proatherogenic mediator release(P<0.05)and aortic remodeling.In vitro,incubation of vascular smooth muscle cells(VSMCs)with AGEs significantly promoted cell proliferation and upregulated the expression of the profilin-1 mRNA and protein(P<0.05).AGEs(200μg/mL,24 h)significantly upregulated the expression of the STAT3 mRNA and protein and JAK2 protein,which was blocked by a JAK2 inhibitor(T3042-1)and/or STAT3 inhibitor(T6308-1)(P<0.05).In addition,pretreatment with T3042-1 or T6308-1 significantly inhibited AGEs-induced RASMC proliferation(P<0.05).CONCLUSION AGEs induce proatherogenic events such as VSMC proliferation,proatherogenic mediator release,and vascular remodeling,changes that can be attenuated by silencing profilin-1 expression.These results suggest a crucial role for profilin-1 in AGEs-induced vasculopathy. 展开更多
关键词 Advanced glycation end products Profilin-1 Diabetic macroangiopathy ATHEROSCLEROSIS vascular remodeling Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway
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Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats
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作者 Gulladawan Jan-On Akarachai Tubsakul +5 位作者 Weerapon Sangartit Poungrat Pakdeechote Veerapol Kukongviriyapan Ketmanee Senaphan Chakree Thongraung Upa Kukongviriyapan 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2021年第1期10-19,共10页
Objective:To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates(SRH)and in combination with lisinopril against hypertension,endothelial dysfunction,vascular remodeling,and oxidative stress in... Objective:To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates(SRH)and in combination with lisinopril against hypertension,endothelial dysfunction,vascular remodeling,and oxidative stress in rats with nitric oxide deficiency-induced hypertension.Methods:Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor,Nω-nitro-L-arginine methyl ester(L-NAME)in drinking water for 6 weeks.Hypertensive rats were administered daily with SRH(500 mg/kg/day),lisinopril(1 mg/kg/day),or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment.Hemodynamic status,vascular reactivity to vasoactive agents,and vascular remodeling were assessed.Blood and aortic tissues were collected for measurements of oxidative stress markers,plasma angiotensin-converting enzyme(ACE)activity,plasma angiotensinⅡ,and protein expression.Results:L-NAME induced remarkable hypertension and severe oxidative stress,and altered contents of smooth muscle cells,elastin,and collagen of the aortic wall.SRH or lisinopril alone reduced blood pressure,restored endothelial function,decreased plasma ACEs and angiotensinⅡlevels,alleviated oxidant markers and glutathione redox status,and restored the vascular structure.The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression.The combination of SRH and lisinopril was more effective than monotherapy.Conclusions:SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system. 展开更多
关键词 Sang-Yod rice bran hydrolysates HYPERTENSION Endothelial dysfunction Oxidative stress vascular remodeling
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Calpain mediated pulmonary vascular remodeling in hypoxia induced pulmonary hypertension
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作者 ZHANG Wei-fang ZHU Tian-tian +2 位作者 GE Xiao-yue XIONG Ai-zhen HU Chang-ping 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1009-1009,共1页
OBJECTIVE To explore the role of calpain in in pulmonary vascular remodeling in hypoxia induced pulmonary hypertension and the underlying mechanism.METHODS Sprague-Dawley rats were randomly divided into hypoxia group ... OBJECTIVE To explore the role of calpain in in pulmonary vascular remodeling in hypoxia induced pulmonary hypertension and the underlying mechanism.METHODS Sprague-Dawley rats were randomly divided into hypoxia group and normoxia control group.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(m PAP)were monitored by the method of right external jugular vein cannula.Right ventricular hypertrophy index was expressed as the ratio of right ventricular weight to left ventricular weight(left ventricle plus septum weight).Level of calpain-1,calpain-2and calpain-4 m RNA in pulmonary artery trunk were determined by real-time PCR.Expression of calpain-1,calpain-2 and calpain-4 protein was determined by Western Blot.Primary rat pulmonary arterial smooth muscle cells(PASMCs)were divided into 4 groups:normoxia control group,normoxia+MDL28170 group,hypoxia group and hypoxia+MDL28170 group.Cell proliferation was detected by MTS and flow cytometry.Level of Ki-67 and PCNA m RNA were determined by real-time PCR.RESULTS RVSP,m PAP and right ventricular remodeling index were significantly higher in the hypoxia group than those in the normoxia group.In the hypoxia group,pulmonary vascular remodeling occurred,and the expression of calpain-1,calpain-2 and calpain-4 m RNA and protein expression was increased in the pulmonary artery.MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs accompanied with decreased Ki-67and PCNA m RNA expression.CONCLUSION Calpain mediated vascular remodeling via promoting proliferation of PASMCs in hypoxia induced pulmonary hypertension. 展开更多
关键词 CALPAIN pulmonary hypertension pulmo-nary vascular remodeling pulmonary arterial smooth muscle cells PROLIFERATION
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Regulation of microRNAs in cell signaling pathways-mediated vascular remodeling
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作者 CHEN Ying SUN Lan DU Guan-hua 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1010-1011,共2页
Vascular remodeling,which can be found in atherosclerosis,restenosis after angioplasty,hypertension,and some other frequent and serious chronic diseases.Smooth muscle cell(SMC)phenotype change,which has been described... Vascular remodeling,which can be found in atherosclerosis,restenosis after angioplasty,hypertension,and some other frequent and serious chronic diseases.Smooth muscle cell(SMC)phenotype change,which has been described as converting from a contractile state into a synthetic phenotype,is a crucial event during vascular remodeling.Recently,micro RNAs(mi RNAs)a kind of small non-coding RNA molecules,has been proven to target critical genes of cell signaling pathways to regulate SMC phenotypic change.By searching the Pub Med,Embase,reviews,and reference listsof relevant papers,we systematically carried out a review of the literature to provide an overview of the mi RNAs and their target genes in cell signaling pathways,focus inthe pathways involving in SMC phenotype change.To be specific,mi RNAs that regulate genes involved in the MAPK signaling pathways(such as:mi R-155,mi R-92a,mi R-424/503,mi R-133,mi R-181b,mi R-31,mi R-1298,mi R-132,mi R-200c and mi R-483-3p),mi RNAs target genes involved in the TGF-βsignaling pathways(including mi R-24,mi R-17/92 cluster,mi R-599,mi R-21 and mi R-143/145),mi RNAs target the genes involved in the AMPK signaling pathways including mi R-144/451 and mi R-195,mi RNAs target the genes involved in the PI3K-Akt signaling pathways(including mi R-138,mi R-34c,mi R-223,mi R-761,mi R-10a,mi R-146a),mi R-199a-5ptargets the genes involved in the Wnt signaling pathways mi RNAs(mi R-221/222,mi R-15b,mi R-24/29a,mi R-224)involved in the PDGF signaling pathways and some mi RNAs(mi R-638,mi R-328,mi R-365,mi R-663,mi R-29b,mi R-130,mi R-142-5p,mi R-424/322)which regulate SMC phenotype change by other corresponding targets were in detailed discussed in our review.Exploring the regulation of miR NAs in key cellsignaling pathways-mediatedvascular remodeling wil have momentous impact on identifying novel therapeutic targets for its associated disease. 展开更多
关键词 MICRORNA vascular remodeling smooth muscle cell cell signaling pathway
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Integrated network pharmacology and experimental verification to explore the mechanism of Sangqi Qingxuan formula against hypertensive vascular remodeling
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作者 Lingling Li Jiayun Wu +4 位作者 Ruiqi Yao Deshuang Yang Ying Chen Jin Zhang Li Huang 《Journal of Traditional Chinese Medical Sciences》 CAS 2022年第3期277-288,共12页
Objective: To investigate the bioactive components of Sangqi Qingxuan formula(SQQX), predict the pharmacological targets, and explore the mechanism of hypertensive vascular remodeling(HVR).Methods: Network pharmacolog... Objective: To investigate the bioactive components of Sangqi Qingxuan formula(SQQX), predict the pharmacological targets, and explore the mechanism of hypertensive vascular remodeling(HVR).Methods: Network pharmacology was adopted to predict how SQQX acts in HVR. The effectiveness was assessed by blood pressure measurements and pathological morphology observation based on a spontaneously hypertensive rat model, while the mechanism of SQQX on HVR was validated by immunohistochemistry(IHC) and western blot(WB) according to the results of network pharmacology.Results: There were 130 bioactive components of SQQX and 231 drug targets predicted by the Traditional Chinese Medicine Systems Pharmacology Database. Subsequently, 181 common targets were identified for SQQX against HVR, with TP53, MAPK1, and AKT1 as the core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses was employed to identify the top 20 enriched functions and the top 20 pathways(P <.01). Finally, the key role of the ERK/MAPK signaling pathway in HVR was determined. The in vivo results suggested that SQQX reduced systolic blood pressure and increased the ratio of thoracic aortic wall thickness to lumen diameter. Additionally, compared with the model group, SQQX increased the expression of smooth muscle 22 alpha(IHC: P <.001;WB:P <.05) and decreased the expression of osteopontin(IHC: P <.001;WB: P <.05), ERK1/2(IHC: P <.001;WB: ERK1 & ERK2, all P <.05), p-ERK1/2(IHC: P <.001;WB: ERK1 & ERK2, all P <.05), and the ratio of pERK1/2 to ERK1/2 protein(IHC: P <.001).Conclusions: SQQX, which has multiple bioactive ingredients and potential targets, is an effective treatment for HVR. The mechanism of antihypertensive and vascular protection may be related to the inhibition of phenotypic transformation of vascular smooth muscle cells and the ERK/MAPK signaling pathway. 展开更多
关键词 Sangqi Qingxuan formula Network pharmacology Hypertensive vascular remodeling Action mechanism Experimental verification Spontaneously hypertensive rats Phenotypic transformation ERK/MAPK pathway
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Regulation and function of cyclic nucleotide phosphodiesterases in pathological vascular remodeling
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作者 YAN Chen 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2017年第5期456-457,共2页
Pathological vascular remodeling is characterized by thickening or thinning of the vessel wall through altering cellular and non-cellular components,which associates with various blood circulation disorders in brain,h... Pathological vascular remodeling is characterized by thickening or thinning of the vessel wall through altering cellular and non-cellular components,which associates with various blood circulation disorders in brain,heart,lung,and peripheral vasculatures. Pathological vascular remodeling occurs in response to a variety of vascular insults such as mechanical(angioplasty or stenting) or biological(lipids,diabetes,smoking,or virus) injuries. It is a polygenic process involving multiple cell types in the vessel wall or circulation,including endothelial cells(ECs),smooth muscle cells(SMCs),fibroblasts,leukocytes,and platelets. One of hallmarks is the transition of vascular smooth muscle cells(SMCs)from a differentiated/quiescent contractile phenotype to a myofibroblast-like dedifferentiated/active so-called synthetic phenotype. Synthetic SMCs are proliferatory,migratory,secretory and inflammatory,playing key roles in the pathogenesis of vascular remodeling. In the normal vessel,ECs synthesize and secrete biological substances such as prostacyclins(PGI_2) and nitric oxide(NO) that not only function as vasodilators but also inhibit SMC phenotype transition and other properties associated with the synthetic phenotype. Cyclic nucleotides cAMP and cGMP are primary mediators of PGI_2 and NO,respectively,and play critical roles in control vascular structural integrity and function. Cyclic nucleotides are controlled by selective activation or inhibition of distinct cyclic nucleotide phosphodiesterase(PDE) isozymes catalyzing the degradation reaction. To date,more than 60 different PDE isoenzymes derived from 22 genes are identified and grouped into 11 broad families(PDE1-PDE11). PDEs are expressed in a cell/tissue-specific manner and only a few enzymes are expressed in any single cell type. Through systematic assessment of the expression levels of all known PDE isoforms in contractile versus synthetic SMCs,we found that the expression levels of a number of PDE are significantly altered between two SMC phenotypes. We then explored the functional roles and underlying mechanisms of these altered PDEs in vascular SMCs pathogenesis and vascular remodeling in vitro and in vivo using a variety of gain-of-or loss-of-function approaches. For example,we found that Ca^(2+)/calmodulinstimulated cAMP/cGMP-hydrolyzing PDE 1C is selectively expressed in synthetic SMCs in vitro and in various vascular disease models in vivo. PDE 1C upregulation contributes to a number of pathogenic functions of synthetic SMCs,such as cell proliferation,migration,and matrix protein metabolism.PDE 1C deficiency markedly attenuates intimal hyperplasia,atherosclerosis,and aortic aneurysm in experimental mouse disease models. These findings suggest that PDE 1C functions as a key regulator of the synthetic SMC pathology in vascular remodeling. Inhibiting PDE 1C function may represent a novel therapeutic strategy for protecting against the pathogenesis of vascular diseases. 展开更多
关键词 PHOSPHODIESTERASES smooth muscle cells vascular remodeling
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Study of Traditional Chinese Medicine in Intervening Vascular Remodeling after Percutaneous Transluminal Coronary Angioplasty
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作者 鹿小燕 徐浩 +1 位作者 史大卓 陈可冀 《Chinese Journal of Integrated Traditional and Western Medicine》 2004年第1期73-77,共5页
Interventional therapy of coronary heart disease (CHD) includes percutaneous transluminal coronary angioplasty (PTCA), stent implantation etc. Owing to its revascularization without cardiac surgery, it has been the ma... Interventional therapy of coronary heart disease (CHD) includes percutaneous transluminal coronary angioplasty (PTCA), stent implantation etc. Owing to its revascularization without cardiac surgery, it has been the main effective method in treating CHD. But at the same time, there exists the problem of restenosis (RS). After PTCA, RS 展开更多
关键词 Study of Traditional Chinese Medicine in Intervening vascular remodeling after Percutaneous Transluminal Coronary Angioplasty MMPS PTCA ECM
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Age-Related Changes of Procollagen Alpha Polypeptide in Vascular Remodeling in Rat Vascular Smooth Muscle Cell
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作者 Minmin Yu Haocheng Zhan +1 位作者 Dalin Song Weili Gai 《Journal of Biosciences and Medicines》 2020年第12期20-31,共12页
The current study revealed that increased synthesis and secretion of collagen types I and III play major roles in arterial wall remodeling, aneurysm formation, and atherosclerotic cap stability. The aim is to investig... The current study revealed that increased synthesis and secretion of collagen types I and III play major roles in arterial wall remodeling, aneurysm formation, and atherosclerotic cap stability. The aim is to investigate the age-related changes of the procollagen alpha polypeptide gene mRNA and protein expression in the vascular smooth muscle cells (VSMCs) in rats, as well as the possible underlying mechanisms. We tested in vitro culture of VSMC from the thoracoabdominal aorta in neonate and 9-month-old healthy male Wistar rats;procollagen alpha polypeptide mRNA and procollagen alpha polypeptide protein expression were detected, using RT-PCR, VG staining, Western blot and ELISA methods. Semi-quantitative analysis displayed that, in the real-time reverse transcription polymerase chain reaction (RT-PCR), the type I collagen α polypeptide chain mRNA increased in the adult group, but not significantly (<em>P</em> = 0.05). Further, there was no significant difference between the two groups of type III collagen α polypeptide chain mRNA (<em>P</em> > 0.05). Both the type I and type III procollagen alpha polypeptide protein expression were increased significantly in the older group as compared with the young group (<em>P</em> < 0.05). This phenomenon mainly lies in the fact that the regulatory pathway on age-related changes of procollagen alpha polypeptides may be one of the molecular mechanisms in vascular remodeling during aging. 展开更多
关键词 AGE-RELATED vascular Smooth Muscle Cell Procollagen Alpha Polypeptide vascular remodeling
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Renovascular hypertension causes cerebral vascular remodeling
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作者 Yamei Tang Xiangpen Li +4 位作者 Yi Li Qingyu Shen Xiaoming Rong Ruxun Huang Ying Peng 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第25期1977-1981,共5页
Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that ... Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia. 展开更多
关键词 cerebral infarction HYPERTENSION renovascular hypertension vascular structural remodeling collateral circulation
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Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling
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作者 GUO Qiru LI Jiali +10 位作者 WANG Zheng WU Xiao JIN Zhong ZHU Song LI Hongfei ZHANG Delai HU Wangming XU Huan YANG Lan SHI Liangqin WANG Yong 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2024年第1期62-74,共13页
Pathological vascular remodeling is a hallmark of various vascular diseases.Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in mod... Pathological vascular remodeling is a hallmark of various vascular diseases.Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular remodeling.Potassium dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections.This study investigates the potential of PDA in regulating pathological vascular remodeling.The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice.Experimental approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions.The results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima formation.PDA treatment significantly increased the proliferation and migration of SMCs.Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular remodeling.Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway. 展开更多
关键词 Potassium dehydroandrographolide succinate Smooth muscle cell Myeloid differentiation factor 88 T-CADHERIN Pathological vascular remodeling
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ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17
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作者 Junting Zhang Yiying Li +9 位作者 Jianchao Zhang Lu Liu Yuan Chen Xusheng Yang Xueyi Liao Muhua He Zihui Jia Jun Fan Jin-Song Bian Xiaowei Nie 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第12期4840-4855,共16页
Pulmonary hypertension(PH)is an extremely malignant pulmonary vascular disease of unknown etiology.ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine,thereby affecting RNA expression.However,the ... Pulmonary hypertension(PH)is an extremely malignant pulmonary vascular disease of unknown etiology.ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine,thereby affecting RNA expression.However,the role of ADAR1 in PH development remains unclear.In the present study,we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling.Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells(PASMCs).Conversely,inhibition of ADAR1 produced opposite effects.High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH.CircCDK17 level was significantly lowered in the serum of PH patients.The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17.ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from mlA modification.We demonstrate for the first time that ADAR1 contributes to the PH development,at least partially,through m1A modification of circCDK17 and the subsequent PASMCs proliferation.Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease. 展开更多
关键词 Pulmonary hypertension ADAR1 Circular RNA vascular remodeling Cell proliferation
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A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling
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作者 Alexander Stahl Dake Hao +8 位作者 Janos Barrera Dominic Henn Sien Lin Seyedsina Moeinzadeh Sungwoo Kim William Maloney Geoffrey Gurtner Aijun Wang Yunzhi Peter Yang 《Bioactive Materials》 SCIE CSCD 2023年第1期167-178,共12页
Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential.Though different tissue enginee... Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential.Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts,it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration.The size of pores within implanted biomaterials has shown significant effects on macrophage polarization,which has been further confirmed as necessary for efficient vascular formation and remodeling.Here,we developed biodegradable,autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts’interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate.The synthetic vascular grafts showed similar mechanical properties to native blood vessels,encouraged macrophage populations with varying M2 to M1 phenotypic expression,and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model.This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases. 展开更多
关键词 vascular graft vascular compliance Pore size Macrophage polarization vascular remodeling
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Mechanistic insight into lysyl oxidase in vascular remodeling and angiogenesis
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作者 Zhao-Jun Wang Qi-Wen Guan +2 位作者 Hong-Hao Zhou Xiao-Yuan Mao Fang-Hui Chen 《Genes & Diseases》 SCIE CSCD 2023年第3期771-785,共15页
Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provide... Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis. 展开更多
关键词 ANGIOGENESIS Disease pathology Lysyl oxidase Therapeutic target vascular homeostasis vascular remodeling
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Effect of probucol on vascular remodeling due to atherosclerosis in rabbits: an intravascular ultrasound study 被引量:12
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作者 LI Ting-ting XIE Yi +4 位作者 GUO Yuan TIAN Hong-bo ZHANG Jian-ning PENG Jie ZHANG Yun 《Chinese Medical Journal》 SCIE CAS CSCD 2011年第12期1840-1847,共8页
Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the ef... Background Probucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis. Methods Aortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks' atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% (wt/wt) probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed. Results Probucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group (56% vs. 21%, 18% vs. 54%, respectively, both P〈0.01). In addition, the probucol group showed a smaller mean remodeling index relative to the control group (0.93 ± 0.13 vs. 1.05 ± 0.16, P 〈0.01). Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S (all P 〈0.01). Conclusions These findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques. 展开更多
关键词 ARTERIOSCLEROSIS intravascular ultrasonography plaque vascular remodeling PROBUCOL
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Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout mice 被引量:7
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作者 XU Yang ARAI Hidenori +2 位作者 MURAYAMA Toshinori KITA Toru YOKODE Masayuki 《Chinese Medical Journal》 SCIE CAS CSCD 2008年第3期220-226,共7页
Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis, postangioplasty restenosis and transplant arteriopathy. Recently, pathologic... Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis, postangioplasty restenosis and transplant arteriopathy. Recently, pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis. But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not yet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene (LDL-/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL -/- mice with the GFP-expressing transgenic mice. LDL-/- mice (22-24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice. Four weeks later, a nonconstrictive cuff was placed around the right femoral artery. After another 2 weeks, both right and left femoral arteries were harvested and subjected to histochemical analysis. Apoptosis was analyzed in situ using TUNEL assay. Results Two weeks after cuff placement, atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells. The tissue stained with anti-α smooth muscle actin (SMA) antibody, showed a number of SMA-positive cells in the intimal lesion area. They were also positive for GFP, indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions. Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP. The intima and media showed a large number of TUNEL-positive signals after 2 weeks cuff injury, indicating the presence of apoptosis in vascular remodeling. Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular injury under the hypercholesterolemic conditions. Our data also clearly indicate that bone marrow-derived cells differentiated to smooth muscles and endothelial cells in the formation of these lesions in the presence of hypercholesterolemia. 展开更多
关键词 vascular remodeling MACROPHAGE smooth muscle cell endothelial cell bone marrow
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