Impact of miRNAs on cardiovascular aging

Aging is a multidimensional process that leads to an increased risk of developing severe diseases, such as cancer and cardiovascular, neurodegenerative, and immunological diseases. Recently, small non-coding RNAs known as microRNAs （miRNAs） have been shown to regulate gene expression, which contributes to many physiological and pathophysiological processes in humans. Increasing evidence suggests that changes in miRNA expression profiles contribute to cellular senescence, aging and aging-related diseases. However, only a few miRNAs whose functions have been elucidated have been associated with aging and/or aging-related diseases. This article reviews the currently available findings regarding the roles of aging-related miRNAs, with a focus on cardiac and cardiovascular aging.

Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ji-Induced Hypertensive Mouse Aortas

Objective AngiotensinⅡ(AngⅡ)-induced vascular damage is a major risk of hypertension.However,the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear.In this study,we explored the novel mechanism associated with Ang Il-induced hypertension.Methods We treated 8-to 12-week-old C57BL/6J male mice with saline and AngⅡ(0.72 mg/kg-d)for 28 days,respectively.Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing.Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot.Functional annotations including Gene Ontology(GO)and Koto Encyclopedia of Genes and Genomes(KEGG)pathway were performed to reveal the molecular mechanism of AngⅡ-induced hypertension.Finally,the differentially expressed genes were validated by using quantitative real-time PCR.Results The result revealed that a total of 773 genes,including 599 up-regulated genes and 174 down-regulated genes,were differentially expressed in the aorta of AngⅡ-induced hypertension mice model.Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the AngⅡ-induced hypertension,including some pathways associated with hypertension such as extracellular matrix,inflammation and immune response.Interestingly,we also found that the differentially expressed genes were enriched in vascular aging pathway,and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased(P<0.05).Conclusion We identify that vascular aging is involved in AngⅡ-induced hypertension,and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.

Targeting of AUF1 to vascular endothelial cells as a novel anti-aging therapy

Background Inhibition of aging of vascular endothelial cells （VECs） may delay aging and prolong life. The goal of this study was to prepare anti-CD31 monoclonal antibody conjugated PEG-modified liposomes containing the AU-rich region connecting factor 1 （AUF1） gene （CD31-PILs-AUF1） and to explore the effects of targeting CD31-PILs-AUF1 to aging VECs. Methods The mean particle sizes of various PEGylated immunoliposomes （PILs） were measured using a Zetasizer Nano ZS. Gel retardation assay was used to confirm whether PILs had encapsulated the AUF1 plasmid successfully. Fluorescence microscopy and flow cytometry were used to quantify binding of CD31-PILs-AUF1 to target cells. Flow cytometry was also used to analyze the cell cycles of aging bEnd3 cells treated with CD31-PILs-AUF1. We also developed an aging mouse model by treating mice with D-galactose. Enzyme-linked immunosorbent assay （ELISA） was used to evaluate the levels of interleuldn-6 （IL-6） and tumor necrosis factor-or （TNF-ct）. The malondialdehyde （MDA） and the superoxide dismutase （SOD） levels were detected by commercial kits. Hematoxylin-eosin （HE） staining was used to determine whether treatment with CD31-PILs-AUF 1 was toxic to the mice. Results CD31-PILs-AUF 1 specifically could targeted bEnd3 VECs and increased the percentage of cells in the S and G2/M phases of aging bEnd3 cells. ELISA showed that content of the IL-6 and TNF-ct decreased in CD31-PILs-AUF1 group. The level of SOD increased, whereas MDA decreased in the CD31-PILs-AUF1 group. Additionally, CD31-PILs-AUF 1 was not toxic to the mice. Conclusion CD31-PILs-AUF 1 targets VECs and may delay their senescence.

Clinical Study on Treatment of Vascular Aging in Patients with Type 2 Diabetes Complicated by Hypertension with Combination of Traditional Chinese Medicine and Western Medicine

Objective:To explore the clinical effect of combination of traditional Chinese medicine and western medicine in treatment of vascular aging in patients with type 2 diabetes complicated by hypertension.Methods:Ninety patients with type 2 diabetes complicated by hypertension admitted to our hospital from May 2016 to August 2019 were selected as research objects.They were randomly divided into control group and observational group,with 45 cases each.Control group was given amlodipine besylate combined with metformin hydrochloride.On the basis of control group,observational group was given combination of TCM syndrome differentiation.Blood glucose,blood pressure and blood lipids before and after 14 days of treatment were compared between two groups.Results:Blood glucose,blood pressure and lipid indexes after treatment were lower than before treatment in both groups;observational group was lower than control group and the difference was statistically significant(P<0.05).Conclusion:Combination of traditional Chinese medicine and Western medicine could lower blood glucose and blood pressure indexes,control blood lipids and delay blood vessel aging in patients with type 2 diabetes complicated by hypertension,it is worthy of clinical popularization.

Research Progress on the Relationship between Vascular Aging and Hypertension

Vascular aging refers to the structural and functional changes of the arterial wall with age.Wscular aging plays an important role in elderly diseases,such as hypertension.Therefore,the relationship between vascular aging and hypertension has attracted extensive attention.This article mainly reviews the mechanism of vascular aging and its influence on hypertension,so as to provide new ideas and directions for the research and prevention of hypertension.

Implications of Klotho in vascular health and disease

Cardiovascular disease(CVD) is a prevalent condition in general population and the first cause of death overall. Klotho, a pleiotropic protein related to longevity that acts as a co-receptor of the fibroblast growth factor 23, has been proposed as a key regulator of the development of CVD. In the few clinical studies made, it has been observed a relationship between low levels of soluble Klotho and the occurrence and severity of CVD, as well as a reduction of cardiovascular risk when they are high. Also, different polymorphisms of human Klotho gene have been related to the incidence of cardiovascular events. Moreover, several experimental studies indicate that this protein acts in the maintenance of vascular homeostasis. Klotho improves endothelial dysfunction through promotion of NO production and mediates antiinflammatory and anti-aging effects such as suppression of adhesion molecules expression, attenuation of nuclear factor-kappa B or inhibition of Wnt signaling. Furthermore,this protein is related to the attenuation of vascular calcification as well as prevention of cardiac hypertrophy. The expression of this protein in the vascular wall implies a new scenario for the treatment of vascular disorders. The purpose of this review is to provide an overview of the relationship between the Klotho protein and CVD, in addition to its role in the maintenance of functional vascular integrity.

Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed regimen, and to analyze baseline risk factors for CNV resolution or recurrence.

Bilateral same-session intravitreal injections of antivascular endothelial growth factors

AIMTo document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.

Comparison of OCT and OCTA manifestations among untreated PCV, neovascular AMD, and CSC in Chinese population

AIM: To compare the qualitative and quantitative features among untreated polypoidal choroidal vasculopathy(PCV), neovascular age-related macular degeneration(nv-AMD) and central serous chorioretinopathy(CSC) using optical coherence tomography(OCT) and OCT angiography(OCTA).METHODS: This retrospective study included 16 eyes with thin-choroid PCV, 18 eyes with thick-choroid PCV, 16 eyes with nv-AMD and 17 eyes with CSC, respectively. The indicators were obtained by OCT and OCTA.RESULTS: Sub-foveal choroidal thickness(SFCT) in CSC was thicker compared to other groups(all P<0.05). SFCT in nv-AMD was thicker compared to thin-choroid PCV, but thinner compared with thick-choroid PCV(both P<0.05). As the ratio of thickness of Haller's layer to thickness of SFCT, which of thin-choroid PCV was significantly higher than CSC(P<0.001). Likewise, thick-choroid PCV had significantly higher ratio than nv-AMD(P=0.016) or CSC(P<0.001). There were differences among them in pigment epithelium detachment(PED). The whole-superficial retinal vessel density(RVD), deep RVD and choroidal capillary vessel density(CCVD) in CSC were significantly higher compared to other three groups, respectively(all P<0.05). The whole CCVD in nv-AMD was higher compared to thick-choroid PCV(P=0.032). Cross-sectional local angiographic form was 87.50%, 83.33%, 0 and 35.29% in thin-choroid PCV, thickchoroid PCV, nv-AMD and CSC, respectively. Cross-sectional diffuse angiographic form was 12.50%, 16.67%, 100% and 5.88% in thin-choroid PCV, thick-choroid PCV, nv-AMD and CSC, respectively.CONCLUSION: Combination of OCT and OCTA can effectively observe the significant alterations existed in PCV, CSC and nv-AMD, and there are distinctive differences among them. The pathogenesis is not exactly the same between PCV and nv-AMD, or PCV and CSC.

Fixed bimonthly aflibercept in nave and switched neovascular age-related macular degeneration patients:one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a retrospective study of 165 eyes with nv AMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCVA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCVA(<15 letters loss) at 12 mo was also evaluated.RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P <0.01). BCVA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P <0.01).Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per year.CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.

Opiate exposure increases arterial stiffness, advances vascular age and is an independent cardiovascular risk factor in females: A cross-sectional clinical study

Background: Whilst several studies have demonstrated poor cardiovascular health in opiate dependence, its role as a cardiovascular risk factor has not been considered. Methods: Pulse wave analysis was undertaken by radial arterial tonometry (SphygmoCor) in female control and opiate-dependent patients and compared to lifetime opiate use. Results: 222 opiate dependent women were compared to 175 controls. Opiate dependent patients were receiving treatment with buprenorphine (83.3%), methadone (13.5%), or naltrexone (3.2%). Non log transformed chronologic age (CA) for the two groups was 33.58 ± 0.57 (opiate) vs. 32.62 ± 0.96 (controls) years (mean ± S.E.M.;P = 0.39). Vascular Reference Age (RA) 39.30 ± 1.28, vs. 35.03 ± 1.41 the RA-CA difference (5.73 ± 1.02 vs. 2.41 ± 0.91) and the RA/CA ratio (1.16 ± 0.03 vs. 1.07 ± 0.02;all P < 0.02), and all measurements of central arterial stiffness (P < 0.02) were significantly worse for opiates compared to controls. When adjusted for CA, RA and central augmentation pressure and index were all worse by themselves and in interaction with CA (all P < 0.005). At 60 years the modelled RA’s were 83.79 and 67.52 years respectively. The opiate dose-duration interaction showed a dose-response effect with RA (P = 0.0033). After full adjustment for established cardiovascular risk factors, the dose-duration interaction remained significant (P = 10-6), was included in 10 other terms, and dose or duration was included in 15 other interactions. Conclusion: These data show that lifetime opiate use is significantly associated with increased arterial stiffness and vascular age and suggest a dose-response relationship. This relationship is robust and persists after full multivariate adjustment. These findings carry far-reaching implications for opiate-induced generalized acceleration of organismal ageing.

Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.

Age-Related Changes of Procollagen Alpha Polypeptide in Vascular Remodeling in Rat Vascular Smooth Muscle Cell

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 (P = 0.05). Further, there was no significant difference between the two groups of type III collagen α polypeptide chain mRNA (P > 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 (P < 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.

Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

AIM:To assess the association between age-related macular degeneration(AMD) and three single nucleotide polymorphisms(SNPS) related to the vascular endothelial growth factor(VEGF) gene.METHODS:The patients who were diagnosed with AMD were included in this prospective study. Three SNPs(rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS:The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group(P =0.072 and P =0.058).However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD(P =0.005 and P =0.010,respectively). One of the SNPs(rs1413711) was also found to be associated with the severity of AMD(P =0.001)with significant genotype distribution between early,intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION:VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

Green Tea Polyphenols Prevent Early Vascular Aging Induced by High-Fat Diet via Promoting Autophagy in Young Adult Rats

Objective Epidemiology studies indicate that green tea polyphenols(GTP)perform a protective effect on cardiovascular diseases,but the underlying mechanisms are complex.The present study aimed to investigate the effect of GTP on high-fat diets(HFD)induced-early vascular aging.Methods Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP(200 mg/kg body weight)for 18 weeks.In vitro experiment,human umbilical vascular endothelial cells(HUVECs)were treated with palmitic acid(PA)and GTP.Results The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD.In addition,the vascular oxidative injury was suppressed following GTP treatment.Furthermore,GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1,and restored SIRT3 expression in the aorta of HFD rats.Consistently,in cultured HUVECs,GTP inhibited cell senescence indicated by SA-β-gal and promoted endothelial autophagy compared with the PA treatment group.The activity of SIRT3 was specifically inhibited by 3-TYP,and the protective effect of GTP was consequently abolished.Conclusion The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.

Valsartan延缓血管内皮细胞衰老及p16^(INK4a)表达变化的研究

目的探讨Valsartan对血管内皮细胞衰老与p16INK4a表达变化的影响,为寻求延缓内皮细胞衰老途径提供理论和实验依据。方法体外培养人脐静脉内皮细胞,予血管紧张素Ⅱ及Valsartan干预,实验分为空白对照组、血管紧张素Ⅱ诱导组及Valsartan组,采用β-半乳糖苷酶(β-gal)染色鉴定细胞衰老;流式细胞术分析细胞周期变化;免疫细胞化学染色法、Western blot分析各组细胞p16INK4a蛋白的表达。结果与对照组比较,血管紧张素Ⅱ诱导组β-半乳糖苷酶阳性染色率显著增多81.24%±6.46%,细胞周期停滞于G0-G1(88.36%±6.45%),p16INK4a蛋白表达水平上调(P<0.05);予以Valsartan干预后,β-半乳糖苷酶阳性细胞染色率减少,G0-G1细胞减少,p16INK4a蛋白表达水平下调(P<0.05)。结论血管内皮细胞衰老分子机制可能通过下调p16INK4a的表达,使细胞周期停滞于G1期有关,Valsartan对血管内皮细胞衰老有一定保护作用,可能通过调控p16INK4a的表达发挥其延缓3血管内皮细胞衰老的作用。

椎间孔镜治疗高龄老年患者腰椎管狭窄合并基础疾病的效果及对VAS、ODI评分的影响

目的:研究椎间孔镜治疗高龄老年患者腰椎管狭窄且合并基础疾病的临床效果及对VAS、ODI评分的影响。方法:选取2015年4月-2017年4月于本院治疗的腰椎管狭窄且合并基础疾病的高龄老年患者88例作为研究对象,按照随机数字表法将其分为观察组和对照组,每组44例。对照组给予常规手术治疗,观察组给予椎间孔镜手术治疗,比较两组的临床效率、手术时间、术中出血量、住院时间和手术结束后12、24、48、72 h的VAS评分,以及接受手术治疗半年后各项ODI评分。结果:观察组的临床治疗有效率为93.18%,明显高于对照组的79.55%,差异均有统计学意义(X^2=5.091,P=0.024)。观察组的手术时间、术中出血量及住院时间均明显少于对照组,差异有统计学意义(P<0.05)。观察组手术治疗结束后12、24、48、72 h的VAS评分,均明显低于对照组,差异均有统计学意义(P<0.05)。观察组接受手术治疗半年后的各项ODI评分均明显低于对照组,差异均有统计学意义(P<0.05)。结论:对于高龄老年的腰椎管狭窄且合并基础疾病的患者,给予椎间孔镜的手术治疗相比常规的手术治疗,可显著改善患者的治疗有效率,可优化患者的各项基础性的手术指征,充分地改善患者的病情,值得临床上的推广。

糖尿病患者嵌甲发生现状及危险因素分析

目的探讨糖尿病患者嵌甲发生状况及危险因素,为临床制订针对性的预防护理措施提供参考。方法2024年1-6月,便利选取上海市某三甲医院糖尿病患者310例。采用嵌甲发生危险因素调查表收集患者相关资料,通过logistic回归分析筛选患者嵌甲发生的危险因素。结果糖尿病患者嵌甲发生率为19.03%;回归分析结果显示,年龄≥60岁、BMI≥24.0 kg/m^(2)、空腹血糖增高、周围血管病变、甲周创伤、甲癣、趾甲修剪不正确以及穿鞋不合适是糖尿病患者嵌甲发生的高危因素(均P<0.05)。结论糖尿病患者嵌甲发生率较高,建议加强对高风险患者的关注,针对危险因素制订预防护理措施,以减少糖尿病患者嵌甲的发生。

VA含量对封装材料EVA老化衰变行为的影响

对同一厂家提供的4种不同醋酸乙烯脂(VA)含量的乙烯-醋酸乙烯酯共聚物(EVA)样品进行室内加速老化实验,通过测试EVA在室内加速老化后的黄变指数、傅里叶变换红外光谱(FTIR)、差示扫描量热曲线(DSC)及热重(TGA)等,研究VA含量对EVA老化衰变行为的影响。结果表明:当VA含量在28%~32%的范围内,与EVA的耐老化性能呈正相关,VA含量越高,EVA的耐老化性能越好;而当VA含量超过32%后,EVA的耐老化性能下降,老化速率加快。