Pulmonary artery stent thrombosis and symptomatic pulmonary hypertension following COVID-19 infection in Alagille patient:A case report

BACKGROUND Alagille syndrome is a multisystem disease that results in various vascular anomalies,commonly involving the cardiac and pulmonary systems.To the best of our knowledge,there is no literature regarding the cardiovascular outcomes of these patients in association with coronavirus disease 2019(COVID-19).CASE SUMMARY A 34-year-old woman with a history of Alagille syndrome who underwent successful atrial septal defect with partial anomalous pulmonary veins and patent ductus arteriosus repair,as well as left pulmonary artery catheterization and stenting in childhood due to pulmonary stenosis.The patient was without any respiratory symptoms and was a dancer prior to contracting COVID-19.Several weeks after her COVID-19 infection,she developed left pulmonary artery stent thrombosis and subsequent symptomatic pulmonary hypertension.A treatment strategy of anticoagulation alongside pharmacological agents for pulmonary hypertension for 3 months followed by balloon pulmonary artery angioplasty to reopen the stenosis was unsuccessful.CONCLUSION In the era of COVID-19,patients with pulmonary vascular malformations and endovascular stents are at an increased risk for chronic thromboembolic disease.Patients may benefit from prophylactic antiplatelet or anticoagulation therapy.Stent thrombosis is a devastating phenomenon and should be treated urgently and aggressively with balloon pulmonary angioplasty,and/or a thrombolytic agent.

Rapid improvement in postpartum pulmonary hypertension associated with hereditary hemorrhagic telangiectasia: A case report and review of literature

BACKGROUND Postpartum pulmonary arterial hypertension(PAH)complicated with hereditary hemorrhagic telangiectasia(HHT)is a rare condition.Diagnosing and treating PAH in patients with HHT can be challenging.To the best of our knowledge,no previous reports have investigated the efficacy of pulmonary vasodilators in improving hemodynamics in postpartum patients with this disease.CASE SUMMARY In this paper,we report a postpartum case of HHT combined with PAH,pre-senting with worsening dyspnea.Genetic testing revealed that the patient carried a heterozygous variant of activin receptor-like kinase 1.The patient received various treatments,including diuretics,anticoagulants,sildenafil,macitentan,inhalation of nitric oxide,and iloprost.Changes in PaO2/FiO2,pulmonary artery systolic pressure as assessed by echocardiography,and N-terminus pro-brain natriuretic peptide levels suggested that,except for iloprost inhalation,the other treatments appeared to have limited efficacy.CONCLUSION To our knowledge,this is the first report on efficacy of pulmonary vasodilators in postpartum patients with HHT and PAH.

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.

The Potential of Circular RNAs as Biomarkers in Pulmonary Arterial Hypertension Related to Congenital Heart Disease

A particular type of endogenous noncoding RNAs known as circular RNAs(circRNAs)has now become possible biomarkers for several diseases because of their stability and tissue-specific expression patterns.CircRNAs might play a role in various of biological processes.The identification of particular circRNAs dysregulated in pulmonary arterial hypertension(PAH)raises the possibility of these molecules serving as biomarkers for the disease’s early diagnosis and treatment.This review mainly summarizes the role and potential of circRNA as a future biomarker in PAH related to congenital heart disease.This study presented several potential circRNA targets as diagnostic biomarkers for PAH,discussed their biological functions,and addressed the challenges that need to be considered for their application in clinical settings.

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.

Pulmonary hypertension post-liver transplant:A case report

BACKGROUND Liver transplantation(LTx)is vital in patients with end-stage liver disease,with metabolic dysfunction-associated steatotic liver disease being the most common indication.Primary sclerosing cholangitis(PSC)is an important indication.Portopulmonary hypertension,associated with portal hypertension,poses a significant perioperative risk,making pretransplant screening essential.CASE SUMMARY We report the case of a 41-year-old woman with PSC who developed severe pul-monary hypertension years after a successful LTx.She presented with worsening dyspnea on exertion and presyncope.Diagnostic evaluation confirmed severe precapillary pulmonary hypertension without evidence of recurrent portal hy-pertension.Initial management with Sildenafil and Macitentan led to a significant improvement in her symptoms,exercise capacity,and biomarkers.This case highlights the rare development of de novo pulmonary hypertension in a liver transplant recipient without recurrent portal hypertension,possibly linked to autoimmune processes or primary liver disease itself.The patient’s positive re-sponse to the combination therapy underscores the importance of prompt diag-nosis and aggressive management.CONCLUSION In conclusion,pulmonary arterial hypertension post-LTx is a rare but serious complication with a poor prognosis,necessitating further research to better understand its mechanisms and to develop effective strategies for prevention and treatment.

Intervention control of aerobic exercise in maintaining quality of life and pulmonary hypertension in hemodialysis patients

BACKGROUND Pulmonary hypertension is a serious complication in the treatment of maintenance hemodialysis patients,which seriously affects the quality of life of patients and threatens their life safety.Prevention,treatment and improvement of pulmonary hypertension are of great significance to improve the quality of life of patients.AIM To investigate the intervention and control of pedal-powered bicycle in maintaining quality of life and pulmonary hypertension in hemodialysis patients.METHODS 73 patients with maintenance hemadialysis combined with pulmonary arterial hypertension at a hemodialysis center in a certain hospital from May 2021 to May 2022 are selected.Patients are divided into two groups,37 cases in the control group(group C)and 36 cases in the intervention group(group I).Patients are divided into two groups,group C is treated with oral administration of betaglandin sodium combined with routine nursing care.Based on group C,group I conducts power cycling exercises.RESULTS After treatment,group I patients had higher muscle strength,36-Item Short Form Health Survey scores,and Kidney Disease Targets Areas scores;The 6-minute walk distance test index level was higher and the Borg score was lower;The group I had lower systolic blood pressure,greater vital capacity,higher positive emotion,lower systolic pulmonary artery pressure index level,higher arterial partial oxygen pressure level,lower pulmonary vascular resistance index level,and higher blood oxygen saturation level[158.91±11.89 vs 152.56±12.81,1795.01±603.18 vs 1907.20±574.15,24.00(22.00,29.00)vs 24.00(22.00,28.00),P<0.001].CONCLUSION Aerobic exercise combined with Western medicine treatment can effectively improve patients'pulmonary hypertension,alleviate their negative emotions,and enable them to achieve a higher level of quality of life.

Independent prognostic value of lipocalin-2 in congenital heart disease-associated pulmonary artery hypertension

BACKGROUND Timely and accurate evaluation of the patient's pulmonary arterial pressure(PAP)is of great significance for the treatment of congenital heart disease.Currently,there is no non-invasive gold standard method for evaluating PAP.AIM To assess the prognostic value of lipocalin-2(LCN2)in relation to PAP in patients with congenital heart disease associated with pulmonary artery hypertension.METHODS We conducted a retrospective analysis of 69 pediatric patients diagnosed with ventricular septal defects.The patients’clinical and laboratory data were collected.The serum LCN2 concentrations were compared between the pulmonary arterial hypertension(PAH)group and the nonPAH group.The correlation of LCN2 concentration with PAH classification was evaluated using binary logistic regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic potential of LCN2 for PAH.RESULTS Serum LCN2 concentration significantly correlated with patients’mean PAP(r=0.544,P<0.001),but not correlated with creatinine(P=0.446)or blood urea nitrogen(P=0.747).LCN2 levels were significantly correlated with PAH in both univariate[odds ratio(OR)1.107,95%CI:1.033-1.185,P=0.004)]and multivariate regression analysis(OR 1.150,95%CI:1.027-1.288,P=0.015).ROC curve analysis revealed an area under the curve of 0.783 for LCN2.At the cutoff value of 19.42 ng/mL,the sensitivity and specificity of LCN2 for diagnosing PAH is 90.19%and 55.56%,respectively.LCN2 concentration also significantly correlated with the post-repair mean PAP in patients with congenital heart disease(r=0.532,P=0.009).CONCLUSION LCN2 is emerging as a candidate biomarker for assessing PAP in patients with congenital heart disease.Its high sensitivity in diagnosing PAH makes it a valuable tool in patient management.

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.

Impact of diabetes mellitus on mortality in pulmonary hypertension:A systematic review and meta-analysis

BACKGROUND Pulmonary hypertension(PH)is a progressive disease characterized by endothelial dysfunction and vascular remodeling and is a leading cause of mortality worldwide.Although it is independently associated with multiple comorbidities,the impact of diabetes mellitus(DM)on mortality in patients with PH remains uncertain.To address this issue,we conducted a systematic review and meta-analysis to investigate the effect of DM on survival in patients with pulmonary hypertension.AIM To investigate the impact of diabetes mellitus on mortality in pulmonary hypertension patients.METHODS We conducted a comprehensive search of four major electronic bibliographic databases like PubMed,Google Scholar,Scopus,and Embase,and identified 106 relevant studies,out of 1561 articles,published since the year 2000 for full-text review.Fourteen retrospective and prospective cohort studies that compared survival between patients with DM and those without DM in the context of PH were deemed eligible for inclusion in our meta-analysis.The study was registered on PROSPERO with the identifier CRD42023390232.RESULTS A total of 116455 patients with PH were included in the meta-analysis,of whom 41228 suffered from DM and 75227 did not.The results of our meta-analysis indicate an elevated mortality rate among PH patients with diabetes mellitus in comparison to those without DM[odds ratio(OR)=1.40,95%CI:1.15–1.70,P=0.0006].The metaregression analysis unveiled a statistically significant negative association between mean age and effect size(coefficient=-0.036,P value=0.018).Conversely,a statistically significant positive association was detected between female proportion and effect size(coefficient=0.000,P value<0.001).CONCLUSION Our meta-analysis,which included approximately 116500 PH patients,revealed that the presence of diabetes mellitus was associated with increased odds of mortality when compared to non-diabetic patients.The metaregression analysis indicates that studies with older participants and lower proportions of females tend to exhibit smaller effect sizes.Clinically,these findings underscore the importance of incorporating diabetes status into the risk stratification of patients with PH with more aggressive monitoring and early intervention to improve prognosis potentially.

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.

Clinical and hemodynamic profiles of elderly patients with pulmonary arterial hypertension： a single center, prospective study

Backgrounds Pulmonary arterial hypertension （PAH） was previously considered an illness that affects mostly the young, but now it is also increasingly recognized in the elderly. The aim of this study was to compare the features of elderly versus younger patients diagnosed with PAH, and to define the prognostic factors which affect their long-term survival. Methods In this prospective, single center study, the clinical, echocardiographic, hemodynamic characteristics, and the outcomes of younger （18-65 years） and elderly （〉 65 years） patients with definitive diagnosis of precapillary PAIl were compared. Results A total of 119 patients were analyzed in this study; 43 were elderly （mean age： 71.5 ± 5.5 years）, while 76 were non-elderly （mean age 44.5 ±15.2 years）. During the mean follow-up duration of 26.8 ±25.0 months, 43 deaths occurred, 17 of which were among the elderly group, with 28 among non-elderly group. Comparison of baseline parameters showed that 6 min walking distance, hemoglobin levels, pulmonary artery pressures and pulmonary vascular resistance were significantly lower; and estimated glomerular filtration rate, body mass index, E/e＇ and pulmonary capillary wedge pressure were significantly higher in the elderly group than in the younger group. Survival analysis demonstrated that the independent predictors of death were tricuspid plane annular systolic excursion （TAPSE; HR： 1.272, 95% CI： 1.079-1.499, P = 0.004） and uric acid （HR： 1.291, 95% CI： 1.042-1.600, P = 0.019） in the elderly group. In contrast, in the non-elderly group, higher brain natriuretic peptide （HR： 1.002, 95% CI： 1.001-1.004, P 〈 0.001） and higher right atrial pressure （HR： 1.128, 95% CI： 1.026-1.241, P = 0.013） values were the only parameters associated with mortality. Conclusions Our data suggest that elderly PAH patients have a unique clinical and hemodynamic profile, with totally different prognostic markers compared to younger PAH patients.

Hematological disorders and pulmonary hypertension

Pulmonary hypertension(PH),a serious disorder with a high morbidity and mortality rate,is known to occur in a number of unrelated systemic diseases.Several hematological disorders such as sickle cell disease,thalassemia and myeloproliferative diseases develop PH which worsens the prognosis.Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction.Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity,activation of proliferative and antiapoptotic pathways leading to vascular remodeling,elevated pulmonary artery pressure,right ventricular hypertrophy and premature death.Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide(NO),limiting its bioavailability,and leading to endothelial dysfunction.In addition,hemolysis releases arginase into the circulation which converts L-arginine to ornithine,thus bypassing NO production.Furthermore,treatments for hematological disorders such as immunosuppressive therapy,splenectomy,bone marrow transplantation,and radiation have been shown to contribute to the development of PH.Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension(PAH).Several studies have reported low iron levels in patients with idiopathic PAH,and iron deficiency is an important risk factor.This article reviews PH associated with hematological disorders and its mechanism:and iron homeostasis and its relevance to PH.

A meta-analysis of soluble suppression of tumorigenicity 2 （sST2） and clinical outcomes in pulmonary hypertension

Suppression of Tumorigenicity 2 （ST2） is a member of the interleukin （IL）-1 receptor family The ST2 receptor exists in two isoforms - ST2 ligand （ST2L） and soluble ST2 （sST2）.ST2L is a membrane receptor and sST2 is a trun- cated receptor which is soluble in the blood, allowing it to be detected in serum. IL-33 is a member of the IL-1 family of ligand and is the fimctional ligand of ST2L receptor. It binds to the ST2L, thereby mediating its immune function.

Pachymic Acid Ameliorates Pulmonary Hypertension by Regulating Nrf2-Keap1-ARE Pathway

Objective:Pulmonary hypertension(PH)is a severe pulmonary vascular disease that eventually leads to right ventricular failure and death.The purpose of this study was to investigate the mechanism by which pachymic acid(PA)pretreatment affects PH and pulmonary vascular remodeling in rats.Methods:PH was induced via hypoxia exposure and administration of PA(5 mg/kg per day)in male Sprague-Dawley rats.Hemodynamic parameters were measured using a right ventricular floating catheter and pulmonary vascular morphometry was measured by hematoxylin-eosin(HE),a-SMA and Masson staining.MTT assays and EdU staining were used to detect cell proliferation,and apoptosis was analyzed by TUNEL staining.Western blotting and immunohistochemistry were used to detect the expression of proteins related to the Nrf2-Keapl-ARE pathway.

The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension

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.

Mesenchymal Stem Cells Attenuate Vascular Remodeling in Monocrotaline-induced Pulmonary Hypertension Rats

Intravenous and intratracheal implantation of mesenchymal stem cells (MSCs) may offer ameliorating effects on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. The aim of this study was to examine the anti-remodeling effect of intravenous MSCs (VMSCs) and intratracheal MSCs (TMSCs) in rats with PH, and the underlying mechanisms. MSCs were isolated from rat bone marrow and cultured. PH was induced in rats by intraperitoneal injection of MCT. One week after MCT administration, the rats were divided into 3 groups in terms of different treatments: VMSCs group (intravenous injection of MSCs), TMSCs group (intratracheal injection of MSCs), PH group (no treatment given). Those receiving saline instead of MCT served as negative control (control group). Pulmonary arterial structure was pathologically observed, pulmonary arterial dynamics measured, and remodeling-associated cytokines Smad2 and Smad3 detected in the lungs, three weeks after MCT injection. The results showed that PH group versus control group had higher pulmonary arterial pressure (PAP) and wall thickness index (WTI) 21 days after MCT treatment. The expression of phosphorylated (p)-Smad2 and the ratio of p-Smad2/Smad2 were much higher in PH group than in control group. Fluorescence-labeled MSCs were extensively distributed in rats’ lungs in VMSCs and TMSCs groups 3 and 14 days after transplantation, but not found in the media of the pulmonary artery. WTI and PAP were significantly lower in both VMSCs and TMSCs groups than in PH group three weeks after MCT injection. The p-Smad2 expression and the ratio of p-Smad2/Smad2 were obviously reduced in VMSCs and TMSCs groups as compared with those in PH group. In conclusion, both intravenous and intratracheal transplantation of MSCs can attenuate PAP and pulmonary artery remodeling in MCT-induced PH rats, which may be associated with the early suppression of Smad2 phosphorylation via paracrine pathways.

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Terlipressin improves pulmonary pressures in cirrhotic patients with pulmonary hypertension and variceal bleeding or hepatorenal syndrome

Terlipressin has been shown to improve both pulmonary and systemic hemodynamics in stable cirrhotic patients with pulmonary hypertension,whereas other vasoconstrictors may cause pulmonary pressures to deteriorate We investigated the pulmonary and systemic hemodynamic effects of the first terlipressin dose(2 mg) in 7 cirrhotic patients with PH presenting with variceal bleeding(n=4) or hepatorenal syndrome(n=3).Terlipressin decreased pulmonary vascular resistance(158.8±8.9 vs 186.5±13.9 dynes sec cm-5 ;P=0.003) together with an increase in systemic vascular resistance(2143± 126 vs 1643±126 dynes sec cm-5 ;P<0.001).Terlipressin should be the vasoconstrictor treatment of choice when patients present with variceal bleeding or HRS.