Risk Stratification and Prognosis of Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Background:Current guidelines for managing pulmonary arterial hypertension(PAH)recommend a risk strati-fication approach.However,the applicability and accuracy of these strategies for PAH associated with congenital heart disease(PAH-CHD)require further validation.This study aims to validate the reliability and predictive accuracy of a simplified stratification strategy for PAH-CHD patients over a three-year follow-up.Additionally,new prognostic variables are identified and novel risk stratification methods are developed for assessing and managing PAH-CHD patients.Methods:This retrospective study included 126 PAH-CHD patients.Clinical and biochemical variables across risk groups were assessed using Kruskal-Wallis and Fisher’s exact tests.Indepen-dent risk factors were identified using ordered logistic regression,while Kaplan-Meier and Cox proportional hazards regression analyses evaluated their impact on all-cause mortality.A new stratification model for the PAH-CHD population was constructed based on these analyses.Results:Significant survival differences across stratified risk groups were observed(p<0.001),validating the effectiveness of the simplified risk stratification method in PAH-CHD patients.Prothrombin activity was a strong independent predictor of adverse outcomes of PAH-CHD patients(Hazard ratio 0.95,p<0.001,C-index 0.70).A model combining N-terminal pro-brain natriuretic peptide,prothrombin activity,albumin,and right atrial area achieved an area under the curve of 0.89 and a C-index of 0.85.Conclusions:The simplified risk stratification method is applicable to PAH-CHD patients.Prothrombin activity is a strong independent predictor of adverse outcomes.A comprehensive risk stratification approach,incorporating both established and novel biomarkers,enhances accessibility and offers predictive efficacy during follow-up for PAH-CHD patients,comparable to established models.

Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome

Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.

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.

Effects of combined aerobic,resistance and inspiratory training in patients with pulmonary hypertension:A systematic review

BACKGROUND Pulmonary hypertension(PH)is a serious progressive disorder of the modern world,characterized by endothelial dysfunction and impaired vasoreactivity.Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity.Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities.However,data regarding the effects of combined exercise training programs in patients with PH still remains limited.AIM To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH.METHODS Our search included all available randomized controlled trials(RCTs)regarding combined aerobic,resistance and inspiratory training programs in patients with PH in 4 databases(Pubmed,PEDro,Embase,CINAHL)from 2012 to 2022.Five RCTs were included in the final analysis.Functional capacity,assessed by peak VO_(2)or 6-min walking test(6MWT),as well as quality of life,assessed by the SF-36 questionnaire,were set as the primary outcomes in our study.RESULTS Peak VO_(2)was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs.Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs(P<0.05).Quality of life was measured in 4 out of 5 RCTs.Although patients improved their quality of life in each group,however,only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls.CONCLUSION By this systematic review,we have demonstrated that combined aerobic,resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH.Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

Pulmonary hypertension,nephrotic syndrome,and polymyositis due to hepatitis C virus infection:A case report

BACKGROUND Hepatitis C infection not only damages the liver but also often accompanies many extrahepatic manifestations.Incidences of pulmonary hypertension(PH)caused by hepatitis C are rare,and incidences of concurrent nephrotic syndrome and polymyositis are even rarer.CASE SUMMARY Herein we describe the case of a 57-year-old woman who was admitted to our department for intermittent chest tightness upon exertion for 5 years,aggravated with dyspnea for 10 d.After relevant examinations she was diagnosed with PH,nephrotic syndrome,and polymyositis due to chronic hepatitis C infection.A multi-disciplinary recommendation was that the patient should be treated with sildenafil and macitentan in combination and methylprednisolone.During treatment autoimmune symptoms,liver function,hepatitis C RNA levels,and cardiac parameters of right heart catheterization were monitored closely.The patient showed significant improvement in 6-min walking distance from 100 to 300 m at 3-mo follow-up and pulmonary artery pressure drops to 50 mmHg.Long-term follow-up is needed to confirm further efficacy and safety.CONCLUSION Increasing evidence supports a relationship between hepatitis C infection and diverse extrahepatic manifestations,but it is very rare to have PH,nephrotic syndrome,and polymyositis in a single patient.We conducted a literature review on the management of several specific extrahepatic manifestations of hepatitis C.

“Treat-Repair-Treat”:Management of Left Main Coronary Compression by a Pulmonary Artery Aneurysm in a Patient with Atrial Septal Defect and Significant Pulmonary Hypertension

Left main coronary compression syndrome(LMCS)may complicate pulmonary artery aneurysms(PAA),usually developed in the context of pulmonary arterial hypertension(PAH).We report the case of a 51-year-old female patient with an atrial septal defect(unsuitable for device closure)complicated by a PAA generating a 90%left main stenosis.The significant PAH held us back from immediate surgery.After specific dual PAH-targeted therapy(sildenafil and bosentan),the atrial septal defect could be closed with a unidirectional valved patch;the PAAinduced LMCS was treated by reductive arterioplasty.The postoperative course was uneventful.Follow-up showed clinical improvement,but PAH treatment was still needed.After three months,coronary angiography showed only an insignificant residual left main stenosis,proving that reductive pulmonary arterioplasty was effective in treating LMCS.Any PAA requires further evaluation for LMCS,a dangerous but treatable complication.The“treat-repair-treat”strategy and shunt-closure with a unidirectional valved patch can both improve surgical prospects of LMCS with shunt-related PAH.

Cardiac amyloidosis presenting as pulmonary arterial hypertension:A case report

BACKGROUND Pulmonary hypertension is a rare cardiopulmonary disease,with an insidious onset that usually worsens rapidly.Amyloid light chain(AL)amyloidosis is a rare systemic disease caused by extracellular deposition of pathologic,insoluble,and proteinaceous fibrils in organs and tissues;however,it is difficult to diagnose given its varied and nonspecific symptoms.To date,rare cases of amyloidosis with pulmonary hypertension have been reported.Of note,the optimal treatments for cardiac amyloidosis complicated with pulmonary hypertension remain unclear.CASE SUMMARY We report a case of a 51-year-old woman who presented with progressively worsening dyspnea.Transthoracic echocardiography indicated severe pulmonary hypertension.Twenty-seven months after first admission,the patient returned with symptoms of progressive heart failure.A myocardial tissue sample stained with Congo red was positive,and the patient was ultimately diagnosed with AL amyloidosis with cardiac involvement.CONCLUSION Although pulmonary hypertension may be idiopathic,it is frequently associated with other conditions.In rare cases,pulmonary hypertension can be a complication of AL amyloidosis,which should be seriously considered in any adult presenting with nonspecific signs or symptoms of cardiac distress.

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.

Pulmonary Hypertension Crisis in Patient with Tetralogy of Fallot and Mixed Total Anomalous Pulmonary Vein Connection after the Primary Correction:A Rare Case Report

Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)compensates for the lack of central pulmonary bloodflow and decreases the severity of right-to-left shunting in TOF.We present a case of a 2-year-old child with complex diagnoses of TOF,TAPVC,a large secun-dum atrial septal defect(ASD),and intraoperatively identified MAPCAs.She underwent surgery to repair the TAPVC,valve-sparing reconstruction of the right ventricular outflow tract,interventricular defect closure,and the creation of patent foramen ovale(PFO).After the operation,hemodynamic instability happened along with sudden blood pressure drop,desaturation,and increased central venous pressure,which subsided after adminis-tering inhalational nitric oxide(NO).A postoperative pulmonary hypertension crisis was suggested when the patient experienced recurrent symptoms after the termination of NO.Echocardiographicfindings of a D-shaped left ventricle(LV),right-to-left PFO shunt and high tricuspid valve gradientfirmly established the diagnosis.It was subsequently managed with continuous NO inhalation and sildenafil,which rendered a satisfactory outcome.Repaired TOF and TAPVC could be at particular risk of developing pulmonary hypertension crisis,especially in the presence of MAPCAs due to possible remodeling of the pulmonary vasculature.Furthermore,a relatively non-compliant LV function and small left atrial size may exacerbate the risk of developing postcapillary pulmonary hypertension after TAPVC repair.A successful postoperative outcome calls for a meticulous preoperative analysis of the anatomical lesions,as well as careful monitoring.

Bosentan Is Associated with a Reduction in Right Ventricular Systolic Pressure N-Terminal Pro-Hormone B-Type Natriuretic Peptide Levels in Young Patients with Pulmonary Hypertension

Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

Twin pregnancy with sudden heart failure and pulmonary hypertension after atrial septal defect repair: A case report

BACKGROUND Pulmonary arterial hypertension(PAH)in pregnancy is one of the major obstetric complications and is considered a contraindication to pregnancy as it is classified as a class IV risk in the revised risk classification of pregnancy by the World Health Organisation.Pregnancy,with its adaptive and expectant mechanical and hormonal changes,negatively affects the cardiopulmonary circulation in pregnant women.Do patients with repaired simple congenital heart disease(CHD)develop other pulmonary and cardiac complications during pregnancy?Can pregnant women with sudden pulmonary hypertension be treated and managed in time?In this paper,we present a case of a 39-year-old woman who underwent cesarean section at 33 wk'gestation and developed PAH secondary to repaired simple CHD.Our research began by a PubMed search for"pulmonary hypertension"and"pregnancy"and"CHD"case reports.Three cases were selected to review PAH in pregnancy after correction of CHD defects.These studies were reviewed,coupled with our own clinical experience.CASE SUMMARY Herein,a case involving a woman who underwent atrial septal defect repair at the age of 34,became pregnant five years later,and had a sudden onset of PAH and right heart failure secondary to symptoms of acute peripheral edema in the third trimester of her pregnancy.As a result,the patient underwent a cesarean section and gave birth to healthy twins.Within three days after cesarean delivery,her cardiac function deteriorated as the pulmonary artery pressure increased.Effec-tive postpartum management,including diuresis,significant oxygen uptake,vasodilators,capacity and anticoagulants management,led to improvements in cardiac function and oxygenation.The patient was discharged from hospital with a stable recovery and transferred to local hospitals for further PAH treatment.CONCLUSION This case served as a reminder to obstetricians of the importance of pregnancy after repair of CHD.It is crucial for patients with CHD to receive early correction.It suggests doctors should not ignore edema of twin pregnancy.Also,it provides a reference for the further standardization of antenatal,in-trapartum and postpartum management for patients with CHD worldwide.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography

BACKGROUND Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension(CTEPH),approximately 20%-29%of patients exhibit a restrictive pattern on pulmonary function testing.AIM To quantify longitudinal changes in lung volume and cardiac cross-sectional area(CSA)in patients with CTEPH.METHODS In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019,we evaluated 15 patients with CTEPH who had chest computed tomography(CT)performed at baseline and after at least 6 mo of therapy.We matched the CTEPH cohort with 45 control patients by age,sex,and observation period.CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test.RESULTS Total,right lung,and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline(total,P=0.004;right lung,P=0.003;right lower lobe;P=0.01).In the CTEPH group,the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group(total,P=0.01;right lung,P=0.007;right lower lobe,P=0.01;CSA,P=0.0002).There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort.CONCLUSION After at least 6 mo of treatment,CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

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.

Research progress in the etiology of pulmonary hypertension

Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands out as the predominant feature in the pathogenesis and pathological alterations of PH.Whereas,the pathogenic factors of PH are intricate,involving multiple interacting elements,and the mechanism behind pulmonary vascular remodeling remains not entirely comprehended.In this context,inflammation,chemokines,and gut microbiota may make a intricate and interrelated difference during the process of pulmonary vascular remodeling.

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

Novel Role of Calcium-Sensitive Receptors in Chronic Hypoxia-Induced Proliferation of Pulmonary Vein Smooth Muscle Cells

Objective:Vascular remodeling due to chronic hypoxia(CH)occurs not only in the pulmonary arteries but also in the pulmonary veins.Pulmonary vascular remodeling arises from the proliferation of pulmonary vascular myocytes.However,the mechanism by which CH induces the proliferation of pulmonary vein smooth muscle cells(PVSMCs)is unknown.This study aimed to investigate the mechanism by which CH affects the proliferation of PVSMCs.Methods:PVSMCs were isolated from rat distal pulmonary veins and exposed to CH(4%O2,60h),and the expression of the calcium-sensitive receptor(CaSR)was detected by Western blotting and immunofluorescence.MTT assay was used to detect the proliferation viability of the cells,and the changes in the intracellular calcium concentration were detected by laser confocal scanning technique.Results:CaSR expression was present in rat distal PVSMCs,and CaSR protein expression was upregulated under hypoxia.The positive regulator spermine not only enhanced CH-induced CaSR upregulation but also enhanced CH-induced increase in cell viability and calcium ion concentration.The negative CaSR regulator NPS2143 not only attenuated CH-induced CaSR upregulation but also inhibited CH-induced cell viability and calcium ion concentration.Conclusion:CaSR-mediated hyperproliferation is a novel pathogenic mechanism for the development of proliferation in distal PVSMCs under CH conditions.

槲皮素调控KCa3.1和NLRP3表达对大鼠PAH右心衰竭的保护作用

目的:测定大鼠心肌组织KCa3.1蛋白、NOD样受体热蛋白结构域相关蛋白3(NLRP3)蛋白,探讨槲皮素对缺氧性肺动脉高压(PAH)右心衰竭的保护作用。方法:选取清洁级雄性SD大鼠40只,分为正常对照组(Control组)、正常槲皮素组(CQ组)、缺氧组(H组)、缺氧槲皮素组(HQ组),每组10只。模型制备成功后,HE染色观察大鼠心肌纤维化情况;麦胚凝集素观察大鼠心肌细胞肥大水平;ELISA检测大鼠血清KCa3.1蛋白表达;Western blotting测定大鼠心肌组织KCa3.1蛋白、NLRP3蛋白表达;超声评估大鼠右心游离壁厚度;计算大鼠右心肥厚指数。结果:槲皮素可以降低PAH大鼠右心室肥厚指数,减轻右心室纤维化,并缓解右心室心肌细胞肥大(P<0.01);Western blotting和ELISA结果显示槲皮素干预可以明显降低心肌KCa3.1和NLRP3的蛋白表达(P<0.01)。结论:槲皮素对缺氧性PAH造成的右心衰竭有保护作用,可能与其抑制大鼠心肌KCa3.1与NLRP3表达有关。

复方葶苈子汤降低COPD-PAH大鼠肺动脉压的机制研究

目的:观察复方葶苈子汤对COPD-PAH大鼠模型氧化应激的影响探讨其可能的机制。方法:采用随机数表法将50只SD大鼠分为正常组、模型组、中药低剂量组、中药中剂量组和中药高剂量组。每日2次,连续2周,分别予复方葶苈子汤低剂量组、中剂量组和高剂量组。分别检测大鼠肺功能、平均肺动脉压力、超氧化物歧化酶(SOD)活力值、丙二醛(MDA)含量、环磷酸腺苷(cAMP)含量、泛素连接酶2(Siah2)mRNA相对表达量、Siah2、A激酶锚定蛋白(Akap121)的蛋白表达水平以及观察肺组织病理形态变化(HE染色法)。结果:与模型组比较中药各剂量组mPAP下降、血清SOD活力值升高、MDA含量下降、cAMP含量升高、AKAP-121蛋白的表达上调(P<0.05);与低剂量组比较中剂量组mPAP升高、血清中SOD活力值升高、MDA含量下降、cAMP含量升高、AKAP-121蛋白的表达上调(P<0.05);与中剂量组比较,高剂量组mPAP降低、SOD活力值升高、MDA含量高剂量组下降、cAMP含量升高、AKAP-121蛋白的表达上调(P<0.05)。结论:复方葶苈子汤可有效降低慢阻肺相关性肺动脉高压大鼠的平均肺动脉压。复方葶苈子汤可以提高大鼠血清中cAMP的含量,可上调血清中SOD活力值对抗COPD大鼠缺氧状态下产生的ROS,降低氧化应激对大鼠肺动脉的影响,减少氧化应激产物MDA的产生。本实验中血清中cAMP含量升高与药物剂量呈正相关,血清中cAMP含量越高Siah2的表达水平下降越明显,AKAP121降解得越少。肺组织中肺动脉血管管壁变薄程度、官腔增大程度与cAMP含量呈正相关。这表明复方葶苈子汤可通过调控cAMP-Siah2-AKAP121通路,减少氧化应激对COPD-PAH大鼠的肺血管壁的损伤,降低肺动脉压。