Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

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.

Arterial Hypertension-Related Factors within Custodial Settings of Southern Benin in 2023

Introduction: Hypertension, a non-communicable disease, is a major public health threat worldwide, accounting for a high level of morbidity and mortality. Although it has been extensively published among the general population, further research is needed to understand the reality of hypertension within the custodial setting. This study aimed to investigate the factors associated with arterial hypertension in custodial settings in southern Benin in 2023. Methods: This was a cross-sectional, descriptive, analytical study held in prisons in southern Benin from March to April 2023, involving inmates selected by two-stage random sampling. In the first stage, four prisons out of the six in the southern region of Benin were selected by simple random sampling. In the second stage, the prisoners were selected by systematic random sampling, with the sampling frame being the numbered list of eligible prisoners in each prison selected. Data collected by observation and questionnaire survey were analyzed using Stata 11 software. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg. Overweight was defined by a body mass index (weight/height2 (kg/m2) ≥ 25. Factors associated with hypertension were identified by multiple logistic regression, at a 5% threshold of significance. Results: Altogether 336 inmates aged 37.55 ± 1.72 years were surveyed. The prevalence of hypertension in custodial settings in southern Benin in 2023 was 31.32% (95% CI [17.06;52.57]). Associated factors were inmate age (ORa = 3.36 95% CI: [1.94;5.85]) and abnormal waist circumference (ORa = 2.61 95% CI [1.27;5.40]). Conclusion: The prevalence of arterial hypertension in prisons of southern Benin (31.32%) is high when compared with the national average (25.9% (22.5-29.3)). The ministries of the Interior and Health need to collaborate to involve inmates in preventive strategies for non-communicable diseases, including hypertension.

Serum Calcium Ionised Rate and Materno-Perinatal Prognosis in Arterial Hypertension in Pregnancy at the Reference General Hospital of Panzi

Hypertensive disorders of pregnancy are among the leading causes of severe maternal morbidity and mortality, particularly in developing countries. Hypertensive disorders of pregnancy are among the leading causes of severe maternal morbidity and mortality, particularly in developing countries, maternal hypocalcaemia being a factor favouring the onset of arterial hypertension during pregnancy. The aim was to determine the maternal and perinatal prognosis of patients with hypertensive disorders of pregnancy as a function of serum ionised calcium levels. Material and Methods: A cross-sectional analytical study of 114 patients with arterial hypertension during pregnancy or during pregnancy or in the postpartum period at the HGR/Panzi from 1 January 2021 to 30 June 2022, text was entered using Microsoft Office Word 2010 and the tables were analysed using Excel 2010. The data was analysed using SPSS version 20.0 and Stata 14.0. The associations of the variables were calculated using Pearson's chi-square test, with a significance threshold set at a value of p < 0.05. Study of risk factors, Odds ratios and their confidence intervals were estimated in a univariate analysis. The most determining factors were identified by multivariate analysis using the Forward conditional logistic regression model. Results: The mean gestational age was 34.43 ± 4.327 amenorheas weeks, 46.6% of patients had a vaginal delivery, 66.65% of which were indicated for maternal prognosis, maternal complications were associated with maternal hypocalcaemia in 81, 82% (P = 0.043) and an OR = 3.255 (P = 0.0158) threefold risk that the patient presenting with a complication is likely to be in a state of hypocalcaemia at 95% confidence index, and fetal prognosis was not significantly related to maternal calcaemia. Conclusion: Maternal hypocalcaemia is one of the factors that can influence maternal-foetal complications maternal-fetal complications, early management and prevention of this pathology is pathology is important to reduce maternal-fetal morbidity and mortality.

Pulmonary arterial hypertension confirmed by right heart catheterization following COVID-19 pneumonia: A case report and review of literature

BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.

Rutaecarpine attenuates monocrotaline-induced pulmonary arterial hypertension in a Sprague-Dawley rat model

Background:Pulmonary arterial hypertension presents with obliterative remodeling of the pulmonary arteries and progressive elevation of pulmonary vascular resistance,which increase the risk of right ventricular failure and death.It has been reported in previous studies that rutaecarpine plays a crucial role in anti-inflammatory and antioxidant activities,which may help regulate cell apoptosis and cell proliferation.The purpose of this study was to determine the effects of rutaecarpine in the rat model of monocrotaline-induced pulmonary hypertension.Methods:We induced pulmonary arterial hypertension in adult Sprague-Dawley rats by injecting monocrotaline(60 mg/kg)and then treated with rutaecarpine(40 mg/kg·d)or sildenafil(30 mg/kg·d)(positive control).Subsequently,pulmonary function,inflammation,cytokines and pulmonary vascular remodeling or proliferation were assessed.Results:Rutaecarpine was found to improve monocrotaline-induced mean pulmonary artery pressure,cardiac index,right heart index,right ventricular hypertrophy index,pulmonary artery remodeling and pulmonary function.reverse transcription-quantitative polymerase chain reaction demonstrated a decrease in tumor necrosis factor-α,interleukin-6 and interleukin-1β,whereas western blots a significantly decrease in the expression of nuclear factor kappa-B,endothelin-1,extracellular signal-regulated kinases 1/2,B cell lymphoma-2,Beclin1 and microtubule-associated protein1 light chain 3-II protein,and increase in the expression of Bax,caspase-3 and p62 protein.Conclusion:Rutaecarpine attenuated pulmonary arterial hypertension by inhibiting inflammation,oxidative stress,cell proliferation and autophagy,while promoting apoptosis.

Atypical Coarctation of the Aorta Revealed by Arterial Hypertension in a 22-Year-Old Young Man

Non-isthmic coarctation of the aorta is a rare congenital malformation in adults. Arterial hypertension is a frequent circumstance of discovery. We reported the case of a 22-year-old Guinean man who had been followed for 5 years for hypertension. Clinically, he presented with hypertension of the upper limbs with a systolic pressure gradient of 100 mmHg. The diagnosis was confirmed by thoracic angioscan, which showed a 65.8% coarctation of the abdominal aorta. He was on triple antihypertensive therapy combining Atenolol 100 mg, Amlodipine 10 mg and Perindopril 10 mg. He is awaiting interventional treatment. His blood pressure is stable at around 140/90 mmHg.

Selexipag as Add-on Therapy for Patients with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease:A Single-Center Retrospective Study

Purpose:This study examined the efficacy and safety of selexipag in treating pulmonary arterial hypertension(PAH)associated with congenital heart disease(CHD).Materials and Methods:We conducted a retrospective study of patients with CHD-associated PAH,treated with selexipag since December 2017.Thirteen adult patients(mean age,45.4 years;women,77%)were treated with selexipag as add-on therapy.Baseline characteristics,World Health Organization functional class,6-minute walking distance(6MWD)test results,N-terminal pro-B-type natriuretic peptide levels,echocardiographic data,and incidence of side effects were assessed.Results:The majority of patients(12/13,92.3%)experienced more than one treatment-associated complication;one patient dropped out of the study due to intolerable myalgia.The results of 6MWD test(from 299.2±56.2 m to 363.8±86.5 m,p=0.039)and tricuspid regurgitation(TR)pressure gradient(from 84.7±20.5 mmHg to 61.6±24.0 mmHg,p=0.018)improved and remained improved after selexipag treatment in 12 patients.Based on the results of a non-invasive risk assessment,8(66.7%)patients showed improvement,3(25.0%)showed no interval change,and the status of one patient(8.3%)deteriorated.Moreover,compared to patients treated with a low dosage,patients treated with a medium-to-high dosage showed a greater increase in 6MWD results(88.3±26.4 m vs.55.3±27.6 m,p=0.043)and a greater reduction in the TR pressure gradient(-33.7±10.9 mmHg vs.-12.5±12.0 mmHg,p=0.015).Conclusion:Selexipag is an efficient pulmonary vasodilator as add-on therapy in treating CHD-associated PAH.

Perioperative Nursing for Adult Congenital Heart Disease with Severe Pulmonary Arterial Hypertension

Objectives: To explore the main points of perioperative nursing for adult congenital heart disease with severe pulmonary arterial hypertension. Methods: A retrospective study of 13 patients with congenital heart disease and severe pulmonary arterial hypertension who admitted to the perioperative period of care from January 2018 to December 2019. To prevent perioperative complications of the patients, the focus is on respiratory and circulatory system care, followed by blood coagulation monitoring, digestive system protection and psychological care. Results: All 13 patients passed the perioperative period and were discharged from ICU. Conclusion: Adult congenital heart disease with severe pulmonary arterial hypertension has high perioperative risk, respiratory and circulatory system care is the key.

Screening key target genes for pulmonary arterial hypertension based on bioinformatics

Background:Screening key target genes for pulmonary arterial hypertension(PAH)based on bioinformatics to provide a reference for the clinical development of drugs to cure PAH.Methods:The keyword“pulmonary arterial hypertension”was used to search related genes in the National Center for Biotechnology Information database(NCBI).The obtained genes data was input to the database of Database for Annotation,Visualization and Integrated Discovery(DAVID)(Version 6.8)to collect relevant information about pathways and genes.And the data of genes were enriched in 37 pathways and genes with occurrence frequency≥10 were respectively imported into the String database to construct protein-protein interaction(PPI)network diagrams,and the two network diagrams were compared.Results:VEGFA,MAPK1,MAPK3,IL6,JUN and TNF were among the highest-ranked genes in two network diagrams.Conclusion:The pathogenesis of PAH is associated with multiple pathways such as the TGF-βsignaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,HIF-1 signaling pathway and so on.The study of VEGFA,MAPK1,MAPK3,IL6,JUN and TNF are closely related to PAH is necessary for us to study further.Through gene interaction network and pathway analysis of disease-associated genes,which will help us to screen the critical target genes of PAH and provide a reference for clinical development of effective drugs for PAH.

Osthole attenuates pulmonary arterial hypertension by modulation of phospholipid metabolism

OBJECTIVE Pulmonary arterial hypertension(PAH)is a malignant pulmonary vascular disease lacking efficacy therapeutics.Therefore,it urgently needs to develop safe and effective drugs for PAH treatment.Osthole derived from Cnidium monnieri(L.)Cusson(Shechuangzi)or Angelica pubescens Maxim(Duhuo)has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats,which is a candidate drug for the prevention of PAH,but the underlying modulatory mechanism is still unclear.Our study aims at investigating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy.METHODS PAH model rats were successfully established with MCT,following osthole administration,then functional metabolomics based on untargeted metabolomics assay,targeted lipidomics analysis,qRT-PCR,Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH.RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate(S1P)was the differential metabolites characterized PAH and reversed by osthole treatment.S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1(Sphk1)and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase.We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH.Then,targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine(C10:2)was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH.C10:2 is the intermediate metabolite of fatty acid oxidation(FAO),and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase.CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase,fatty acid synthase,phospholipase A2,carnitine palmitoyltransferase 1A to inhibit C10:2,thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosynthesize necessary essence for pulmonary artery smooth muscle cells(PASMCs)proliferation.Moreover,we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling.Therefore,osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.

NOTCH3 Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.

Discharge planning for children with ventricular septal defect and pulmonary arterial hypertension in China

Objective:To evaluate the effectiveness of discharge planning on maternal caring knowledge,maternal caring behavior,maternal discharge readiness and the rehospitalization of children with ventricular septal defect and pulmonary arterial hypertension(VSD-PAH).Background:Children with congenital heart disease(CHD)with pulmonary arterial hypertension(PAH)have more complications after surgery than those without PAH.Discharge planning is an effective strategy to help children leave the hospital safely,and receive appropriate care after discharge.Methods:A quasi-experimental design was used.Sixty children and their mothers were recruited and divided into two groups:the control group received conventional care,the intervention group received both conventional care and additional discharge planning care.Results:(1)After admission,maternal caring knowledge between the two groups was similar.(2)At discharge,maternal discharge readiness,maternal caring knowledge and maternal caring behavior in the intervention group was significantly higher compared to the control group(t=3.35,p=0.001;F=84.74,p<0.001;F=23.82,p<0.001).This difference persisted after discharge,and was evident at one month and three months after discharge.(3)However,no significant difference in the readmission rate of children after discharge was evident between the two groups.Conclusions:Discharge planning improves the maternal discharge readiness,maternal caring knowledge and maternal caring behaviors.However,this planning did not reduce the readmission rate of children with CHD-PAH.

Prognostic value of the echocardiographic right/left ventricular end-diastolic diameter ratio in patients with idiopathic pulmonary arterial hypertension

Background Previous studies have shown that an echocardiographic right/left ventricular end-diastolic diameter ratio(RV/LV ratio)≥0.9 is an independent predictor of poor prognosis in patients with acute pulmonary embolism. The prognostic value of the RV/LV ratio in patients with idiopathic pulmonary arterial hypertension(IPAH) is still unknown. Methods We retrospectively enrolled 95 consecutive patients with newly diagnosed IPAH and 16 of them were reevaluated by echocardiography at 3-12 months following targeted therapy.Follow-up data were obtained by telephone interviews and review of the patients’ records.Results The RV/LV ratio was in parallel with the severity of World Health Orgnization(WHO) functional class and mean right atrial pressure.The RV/LV ratio was positively correlated with total pulmonary resistance(P P P 2 saturation(P P = 0.001),weight and absence of targeted therapy were independent predictors of death.No significant changes in the RV/LV ratio before and after targeted therapy were observed. A baseline RV/LV ratio≥0.84 or a further increase in the RV/LV ratio during targeted therapy indicated a poor prognosis. Conclusions The RV/LV ratio helps to assess the severity of IPAH and serves as an independent predictor of prognosis in patients with IPAH.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease

BACKGROUND Despite major advances in pharmacologic treatment,patients with pulmonary arterial hypertension(PAH)still have a considerably reduced life expectancy.In this context,chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH,thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIM To evaluate the application and prognostic effect of neurohormonal inhibitors(NEUi)in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODS We analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1,2005 to October 31,2018.Patients on beta-blocker,angiotensin-converting enzyme inhibitor,angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi nonrecipients.RESULTS Complete data were available for 57 PAH subjects:27 of those(47.4%)were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients.NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients.Additionally,NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients(56.7%vs 25.9%,log-rank P=0.020).CONCLUSION The above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival.Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

Efficiency of Esmolol in Treating Postoperative Arterial Hypertension in Patients with Ischemic Heart Disease

To investigate the efficiency and safety of(β+α)-adrenoblocker esmolol for postoperative arterial hypertention(PAH)in patients with ischemic heart disease.The study included 25 patients(45-65 years,mean age 51.5±7.3)who underwent coronary artery bypass grafting surgery with continuous blood purification(CPB).PAH developed during first post-op hours,all patients were ventilated with 2-4 scale sedation by RASS.All patients had arterial hypertension and were on constant therapy.Esmolol was administered IV push 20 mg within a minute.When required,injection was repeated in 5 min until full required effect.Maximum dose was 100 mg.For intraoperative treatment of hypertension 80 mg bolus within 30 sec was injected followed by 150 mg/kg/min infusion when required.Post-op dosage was administered similarly.Esmolol treatment was efficient in 82.6%of cases.Most frequent target AH was achieved using up to 40 and 60 mg in 20%and 36.9%of cases accordingly.Antihypertension effect maintained within 24 hours after injection.Esmolol cause moderate reduction of heart rate(4-7%),making it possible to use in case of hypertension without tachycardia.It is well tolerated and safe as no side effects were observed.The study showed high efficiency and safety of using esmolol to manage post-op arterial hypertension in cardiac surgery patients.

Ventricular Repolarization: Epidemiology and Clinical Correlates among Type-2 Diabetics with Uncontrolled Arterial Hypertension in Western Region of the Republic of Macedonia

This study aimed to describe the epidemiology of repolarization dispersion (QT dispersion and Tpeak-Tend dispersion) and further describe their associated clinical correlates among uncontrolled arterial hypertension in type-2 Diabetics patient, in western region of the Republic of Macedonia. Abnormal ventricular repolarization is associated with increased cardiovascular risk. Data relating to the frequency of increased repolarization dispersion, among uncontrolled arterial hypertension in type-2 Diabetics patient in western region of the Republic of Macedonia, are scarce. A total of 600 patients were enrolled into this observation study. Study participans were selected among primary care patient, who were receiving ongoing care for diabetes mellitus and hypertension during 1 calendar year. Twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersions, were determined manually, and were compared between groups. Patients with uncontrolled BP have greater frequency of: prolonged QTc.max.interval, (61.3% vs.33.6%;p = 0.0005), prolonged Tpeak-Tend interval (65.3% vs. 34.7%;p = 0.005), increased dispersion of QTc. interval (65.9% vs. 34.1%;p = 0.00), increased disperion of Tpeak-Tend interval (65.5% vs. 34.5%;p = 0.002). Females with uncontrolled BP have greater frequency of: increased dispersion of QTc. interval (61.2% vs. 38%;p = 0.02), increased dispersion of Tpeak-Tend interval (63.1% vs. 31.5%;p = 0.008). Hypertensive diabetic patients with uncontrolled BP and abnormal ventricular repolarization have greater BMI (p = 0.000;95%CI 3.849 - 7.871), longer duration of D.M (p = 0.000;95%CI 1.600 - 1.981), longer duration of arterial hypertension (p = 0.000;95%CI 1.468 - 1.850) and less controlled glycemia (p = 0.000;95%CI 1.556 - 3.004). Frequency of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization among diabetic patients with uncontrolled BP, is considerable high and seems to be significantly associated with demographic and clinical parameters: gender, BMI, duration of diabetes, duration of BP and glycemic control.

Treatment of patients with bosentan in postoperation of congenital heart disease with pulmonary arterial hypertension:a double-blind,randomized controlled trial

Objective Endothelin is a key role in the pathogenic of pulmonary arterial hypertension. High concentrations of endothelin 1 have been recorded in plasma and lungs of patients with pulmonary artery hypertension associated with congenital heart disease,and the concentrations of endothelin-1 was correlated with severity degree

Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

OBJECTIVE The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling,which is characteristic of pulmonary arterial hypertension(PAH).In this study we exam-ined whether salvianolic acid A(SAA)extracted from the traditional Chinese medicine′Dan Shen′attenuated vascular remodeling in a PAH rat model,and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg-1,sc).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive control bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA or bosentan effectively ameliorated MCTinduced pulmonary artery remodeling,pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal injury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphogenetic protein typeⅡreceptor(BMPRⅡ)and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRⅡ-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the patients at high risk of PAH.

A Network Meta-analysis of the Efficacy and Safety of Targeted Drug Combinations in the Treatment of Pulmonary Arterial Hypertension

Objective:This network meta-analysis aims to compare the efficacy and safety of different targeted drug combination treatment for pulmonary arterial hypertension(PAH).Methods:Searches were conducted in Cochrane,PubMed,EMBASE,China National Knowledge Infrastructure,China Biomedical Literature Database,Wanfang Database,and ViP Chinese Science and Technology Journal Data to identify both published and unpublished randomized controlled trials from inception until January 1,2022.The risk of bias in the included studies was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions.A network metaanalysis was performed using Stata 16.0 software.The efficacy and safety of different targeted drugs combined treatment for PAH were evaluated based on forest plot,funnel plot,and surface under the cumulative ranking.Results:A total of 29 randomized controlled trails with 4,448 patients treated with 10 different types of targeted drug combinations were included in this study.The results of the surface under the cumulative ranking showed that the combination regimen was the best clinical option to improve symptoms and delay progression in patients with pulmonary artery hypertension compared with monotherapy.Sildenafil in combination with ambrisentan significantly improved the 6-minute walk distance and reduced N-terminal pro-brain natriuretic peptide levels.Bosentan in combination with sildenafil significantly reduced mean pulmonary artery pressure,whereas bosentan in combination with epoprostenol was more effective than other combinations in reducing pulmonary vascular resistance.Bosentan in combination with tadalafil significantly improved the Borg dyspnea score,and bosentan in combination with iloprost was the best combination for improving World Health Organization functional class/New York Heart Association functional class.In terms of safety,there was no significant reduction in the incidence of adverse events,hospitalizations,or allcause mortality for combination therapy compared with monotherapy.Bosentan combined with sildenafil significantly reduced the risk of serious adverse events,but the risk of discontinuation due to an adverse event was higher than monotherapy.Sildenafil combined with epoprostenol reduced the risk of clinical worsening in patients with PAH.Conclusion:Compared with monotherapy,targeted drug combinations for PAH significantly improves exercise tolerance,pulmonary hemodynamic parameters,and reduces the risk of serious adverse events and clinical worsening in patients.Bosentan in combination with sildenafil and bosentan in combination with iloprost are combinations of targeted agents with significant efficacy and better safety profile than monotherapy for the treatment of PAH.Sildenafil in combination with epoprostenol has a low risk of clinical worsening in PAH.

Bioinformatics Analysis of the Regulatory lncRNA–miRNA–mRNA Network and Drug Prediction in Patients with Pulmonary Arterial Hypertension

Objective:Pulmonary arterial hypertension(PAH)is a cardiovascular disease caused by primary proliferative lesions in pulmonary arterioles.Competing endogenous RNAs(ceRNAs)have been reported to act as sponges for microRNAs(miRNAs).To date,however,the mechanisms underlying ceRNA involvement in PAH have not been investigated.This study aimed to construct a PAH-related ceRNA network to further explore the mechanisms of PAH.Methods:A probe reannotation was conducted to identify the long non-coding RNAs(lncRNAs)and messenger RNAs(mRNAs)involved in PAH.Based on the reannotation results,the“limma”package was used to identify the differentially expressed genes(DEGs)and lncRNAs.The miRcode database was used to predict the lncRNA–miRNA interactions.Then,the mRNAs targeted by the miRNAs were predicted by using TargetScan,miRTarBase,and miRDB.Based on the above interactions,a ceRNA network was constructed,which was mapped and visualized with Cytoscape 3.6.1 software.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the database.To predict possible drugs or molecules that may mitigate PAH,C-Map analysis was applied to find relevant molecular compounds that can reverse the expression of DEGs in cell lines.Results:The ceRNA network consisted of 174 nodes and 304 links,which included 10 lncRNAs,23 miRNAs,and 53 mRNAs.The hub genes of the ceRNA network for PAH included hsa-miR-17-5p,hsa-miR-20b-5p,MEG3,HCP5,hsa-miR-27a-3p,hsa-miR-107,hsa-miR-142-3p,hsa-miR-363-3p,hsa-miR-301b-3p,and hsa-miR-23b-3p.Calprotectin,irinotecan,and medrysone were found to be the 3 significant compounds.Conclusion:This study found that hsa-miR-17-5p,hsa-miR-20b-5p,MEG3,HCP5,hsa-miR-27a-3p,hsa-miR-107,hsa-miR-142-3p,hsa-miR-363-3p,hsa-miR-301b-3p,and hsa-miR-23b-3p maybe the underlying biomarkers and targets for diagnosis and treatment of PAH.