Changes of Protein Kinase Cα and Cyclin D1 Expressions in Pulmonary Arteries from Smokers with and without Chronic Obstructive Pulmonary Disease

The purpose of this study was to investigate the changes of protein kinase Ca （PKCα） and cyclin D1 expressions in pulmonary arteries from＇smokers with normal lung function and smokers with mild to moderate chronic obstructive pulmonary disease （COPD）. The peripheral lung tissues were obtained from 10 non-smokers with normal lung function （non-smoker group）, 14 smokers with normal lung function （smoker group）, 11 smokers with mild to moderate COPD （COPD group）. The morphological changes of pulmonary arteries were observed by HE-staining. The expressions of ct-smooth muscle actin （α-SMA）, proliferating cell nuclear antigen （PCNA）, PKCα and cyclin D1 proteins in pulmonary artery smooth muscle cells （PASMCs） were immunohistochemically determined. The percentages of PCNA-positive cells were taken as the smooth muscle cells proliferation index （PI）. The mRNA expressions of PKCα and cyclin D l in PASMCs were evaluated by real-time fluorescence PCR. Morphometrical analysis showed that the ratio of pulmonary artery wall area to total area （WA%） in smoker group and COPD group was significantly greater than that in non-smoker group （P〈0.01）. The PASMCs proliferation index in smoker group and COPD group was significantly higher than that in nonsmoker group （P〈0.01）. The protein levels of PKCct and cyclin D1 inPASMCs were significantly increased in smoker group and COPD group as compared with non-smoker group （P〈0.01）. The mRNA expressions of PKCα and cyclin D1 in PASMCs were significantly elevated in smoker group and COPD group as compared with non-smoker group （P〈0.01）. Significant correlations were found between PKCα protein and WA% or PI （P〈0.01）. Correlations between cyclin D1 protein and WA% or PI also existed （P〈0.01）. The expression of PKCa was positively correlated with the expression of cyclin D 1 at both protein and mRNA levels （P〈0.01）. In conclusion, increased expressions of PKCα and cyclin D1 might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with normal lung function and smokers with mild to moderate COPD.

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.

Effects of nitric oxide and hydrogen sulfide on the relaxation of pulmonary arteries in rats

Background The balance between vasodilation and vasoconstriction plays a major role in maintaining vascular homeostasis. However, the underlying mechanisms are unclear. More and more evidence suggested that there was an interaction in the regulation of vasorelaxation between nitric oxide （NO） and hydrogen sulfide （H2S）. We explored the interaction between and effects of NO and H2S on the relaxation of pulmonary arteries in rats. Methods Seven male Sprague-Dawley rats were anaesthetized with chloral hydrate and the pulmonary arteries of each rat separated for the study of vascular activities. The vasorelaxing activities of pulmonary artery rings in response to different doses of a NO donor, sodium nitroprusside （SNP）, or a H2S donor, sodium hydrogensulfide （NariS）, were measured in vitro. When pulmonary artery rings were treated with a cystathionine-y-lyase inhibitor, DL-propargylglycine, in the presence of SNP or a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester, in the presence of NariS, the changes in relaxing activities were analyzed. Results The relaxation of pulmonary artery rings was in a dose dependent manner in response to either SNP or NariS. The relaxation rates of pulmonary artery rings increased from （30.90±4.62） % to （60.50±8.08） % when the concentration of SNP increased from 1 pmol/L to 3 pmol/L and from （26.13±4.12） % to （53.09±14.01） % when the concentration of NariS increased from 25 pmol/L to 100 μmol/L. However, when appropriate inhibitor was added, the relaxation responses to SNP and NariS decreased. Conclusions The results suggested that similarly to NO, H2S acted as a vasorelaxant either independently of, or synergistically with NO in the regulation of vasorelaxation. The interaction between NO and H2S played an important role in regulating relaxing activities of pulmonary arteries.

Alleviating experimental pulmonary hypertension via co-delivering FoxO1 stimulus and apoptosis activator to hyperproliferating pulmonary arteries

Pulmonary hypertension(PH)is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated.The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells(PASMCs)contributes to pulmonary vascular remodeling in pulmonary hypertension,which is closely linked to the downregulation of forkhead box transcriptional factor O1(FoxO1)and apoptotic protein caspase 3(Cas-3).Here,PA-targeted co-delivery of a FoxO1 stimulus(paclitaxel,PTX)and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension.The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles,followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs.The co-loaded system(170 nm)circulates in the blood over time,accumulates in the lung,effectively targets the PAs,and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics,leading to a decrease in pulmonary arterial pressure and Fulton's index.Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis.Taken together,this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

Clinical results of combined palliative procedures for cyanotic congenital heart defects with intractable hypoplasia of pulmonary arteries

Background Congenital heart defects with intractable hypoplasia of the pulmonary arteries without intercourse or with intercourse stenosis is unsuitable for surgical correction or regular palliative procedures. We reported our experience with combined palliative procedures for congenital heart defects with intractable hypoplasia pulmonary arteries. Methods From 2001 to 2012, a total of 41 patients with cyanotic congenital heart defects and intractable hypoplasia of the pulmonary arteries underwent surgical procedures. From among them, 31 patients had pulmonary atresia with ventricular septal defect （VSD） and the other 10 cases had complicated congenital heart defects with pulmonary stenosis. Different kinds of palliative procedures were performed according to the morphology of the right and left pulmonary arteries in every patient. If the pulmonary artery was well developed, a Glenn procedure was performed. A modified Blalock-Taussig shunt or modified Waterston shunt was performed if pulmonary arteries were hypoplastic. If the pulmonary arteries were severely hypoplastic, a Melbourne shunt was performed. Systemic pulmonary artery shunts were performed bilaterally in 25 cases. A systemic-pulmonary shunt was performed on one side and a Glenn procedure was performed contralaterally in 16 cases. Major aortopulmonary collateral arteries were unifocalized in six cases, ligated in two cases and interventionally embolized in two cases. There was one early death because of cardiac arrest and the hospital mortality was 2.4%. Results Five patients suffered from postoperative low cardiac output syndrome, three had perfusion of the lungs, and two pulmonary infections. Systemic pulmonary shunts were repeated after the original operation in three cases due to the occlusion of conduits. The mean follow-up time was 25 months. The pre- and the post-operation left pulmonary indices were （8.13±3.68） vs. （14.9±6.21） mm2/m2. The pre- and post-operation right pulmonary indices were （12.7±8.13） vs. （17.7±7.78） mm2/m2. The pre- and post-operational pulmonary indices were （20.87±9.43） vs. （32.6±11.7） mm2/m2. They were all significantly increased （P 〈0.001）. The diameter of the pulmonary artery increased after the modified Blalock-Taussig shunt （（5.51±0.94） mm2/m2 pre-operation vs. （7.01±1.97） mm2/m2 post-operation）, the modified Waterston shunt （（5.70±3.96） mm2/m2 pre-operation vs. （9.17±3.62） mm2/m2 post-operation） and the Melbourne shunt （（2.17±0.41） mm2/m2 pre-operation vs. （7.35±2.49） mm2/m2 post-operation） （all P 〈0.05）. Bilateral pulmonary arteries developed well as compared to their pre-operation development. Hemoglobin decreased from （194±27） to （174±24） g/L （P 〈0.05） and peripheral oxygen saturation increased from （65±11）% to （84±6）% （P 〈0.001 ）. During the follow-up of 27 to 49 months, ultimate complete repair was performed in four cases and one patient underwent a Glenn procedure. Conclusions The procedures should be considered on a case to case basis in patients having hypoplasia of the pulmonary arteries with cyanotic congenital heart defects. Combined palliative operations could be an adequate strategic treatment.

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.

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.

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.

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.

Migration of a Progestin Implant into a Pulmonary Artery: Observation of a Case at the Reference Health Center of Commune III of the District of Bamako in Mali

It was a 36-year-old patient, 5th Pregnancy, 5th Delivery, 4 live children, and I deceased, had a consultation in the department for the removal of implants. Questioning revealed that she had had the implant three years ago without medical follow-up. It was in view of the difficulties in extracting the capsule that the chest X-ray and CT scan carried out concluded that the implant had migrated into a branch of the left pulmonary artery. Therapeutic abstention has been the attitude of cardiovascular surgeons.

Iptakalim, a novel ATP-sensitive potassium channel opener, inhibits pulmonary arterial smooth muscle cell proliferation by downregulation of PKC-α

Iptakalim is a new ATP-sensitive potassium （KATp） channel opener, and it inhibits the proliferation of pulmonary arterial smooth muscle cells （PASMCs） and pulmonary vascular remodeling. However, the underlying mechanism remains unclear. In the present study, we found that iptakalim significantly decreased pulmonary artery pressure, inhibited pulmonary ariery remodeling and PKC-α overexpression in chronic hypoxia in a rat pulmonary hypertension model. Iptakalim reduced hypoxia-induced expression of PKC-α, and abolished the effect of hypoxia on PASMC proliferation significantly in a dose-dependent manner in vitro. Moreover, these effects were abol- ished by glibenclamide, a selective KArp channel antagonist. These results indicate that iptakalim inhibits PASMC proliferation and pulmonary vascular remodeling induced by hypoxia through downregulating the expression of PKC-α. Iptakalim can serve as a novel promising treatment for hypoxic pulmonary hypertension.

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.

Saddle pulmonary embolism is not a sign of high-risk deterioration in non-high-risk patients: A propensity score-matched study

BACKGROUND: There is controversy regarding whether saddle main pulmonary artery(MPA) embolism represents a high risk of deterioration in non-high-risk acute pulmonary embolism(PE) patients. This study aims to address this issue by conducting a propensity score matching(PSM) study.METHODS: A total of 727 non-high-risk acute PE patients were retrospectively evaluated. We evaluated the Bova score and risk stratification to examine the risk of deterioration. Deterioration defined as any adverse event within 30 days after admission. Computed tomographic pulmonary angiography was used to identify the embolism type. All patients were matched into four subgroups by PSM according to age, sex, Bova score, and risk stratification:(1) MPA and non-MPA embolism;(2) non-saddle MPA and non-MPA embolism;(3) saddle MPA and non-saddle MPA embolism;(4) saddle MPA and non-MPA embolism. Correlations were analyzed using Cox regression analysis, and deterioration risk was compared between subgroups using Kaplan-Meier analysis.RESULTS: Cox regression analysis revealed that MPA embolism was correlated with deterioration, regardless of whether saddle MPA embolism was included or excluded. Saddle MPA embolism was not correlated with deterioration, regardless of comparison with non-saddle MPA embolism or non-MPA embolism. Patients with MPA and non-saddle MPA embolism presented a high risk for deterioration(logrank test=5.23 and 4.70, P=0.022 and 0.030, respetively), while patients with saddle MPA embolism were not at a high risk of deterioration(log-rank test=1.20 and 3.17, P=0.729 and 0.077, respetively).CONCLUSIONS: Saddle MPA embolism is not indicative of a high risk of deterioration in nonhigh-risk acute PE patients.

THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group（ 10％ O2, 8h/d） and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling（ TUNEL） technique was used to detect nucleosomal DNA fragmentation of apoptotic cells. In situ hybridization and RT- PCR were used to detect the expression level of bcl- 2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT- PCR, we found the expression of bcl- 2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bcl- 2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

Quercetin attenuates the progression of monocrotaline-induced pulmonary hypertension in rats

Pulmonary arterial hypertension （PAH） is a progressive disease associated with increased constriction and remodeling of the pulmonary vasculature. Quercetin is a natural fiavonoid and has a variety of pharmacological effects including improvement of endothelial cell function. However, its pharmacological effects on pulmonary hypertension have been rarely reported. We sought to observe the protective effect of quercetin in rats with monocrotaline induced PAH. We divided 30 male Sprague-Dawley rats randomly into three groups with ten rats in each group： the monocrotaline group, the quercetin group and the control group. We found that, compared with the controls, the mean pulmonary artery pressure （mPAP） and the right ventricular hypertrophy index in the monocrotaline group were significantly higher （P 〈 0.01）. Quercetin caused a significant reduction both in the mPAP and fight ventricular hypertrophy index compared with the monocrotaline group （P 〈 0.01） while no difference was found between the quercefin group and the control group （P 〉 0.05）. Monocrotaline induced a marked increase in the wall thickness （WT） in small and mid-sized pulmonary arteries compared with the controls （P 〈 0.01）. Monocrotaline also induced a marked increase in the wall area （WA） in small [（56.38 ±6.65）% in monocrotaline vs. （19.80±4.63）% in control] and mid-sized [（43.71± 5.38）% in monocrotaline vs. （14.24± 3.66）% in control] pulmonary arteries （P 〈 0.01）. Quercefin treatment markedly reduced monocrotaline induced increase in both WT and WA （P 〈 0.01）, which, however, still remained significantly elevated compared with those of the controls （P 〈 0.01）. Furthermore, compared with controls, proliferating cell nuclear antigen （PCNA） expression in the pulmonary artery tissues was markedly increased by monocrotaline [（45.59± 1.27） in monocrotaline vs. （9.64± 0.69） in controls], which was significantly attenuated by quercetin. Our animal experiment indicated that quercetin could have protective effects on monocrotaline-induced PAH.

Anomalous origin of left pulmonary artery branch from the aorta with Fallot's tetralogy:one case report

We report the case of a ten-year-old boy who had often presented with respiratory distress since born. Chest X-ray showed an enlarged right ventricle. Echocardiography demonstrated characteristic features of Fallot＇s tetralogy and the left pulmonary artery could not be visualized. However, cardiac catheterization disclosed that the left pulmonary artery had an anomalous origin in the ascending aorta. The patient underwent total surgical correction of the defects. Nine days later, he was discharged. We present the results of a literature review of the incidence, physiopathological, clinical, diagnostic, and surgical characteristics of this rare disease.

ERK1/2 Promotes Cigarette Smoke-induced Rat Pulmonary Artery Smooth Muscle Cells Proliferation and Pulmonary Vascular Remodeling via Up-regulating CyclinE1 Expression

Summary： This study iflvestigated the potential role of ERK1/2-cyclinE1 signaling pathway in rat pulmonary artery smooth muscle cells （rPASMCs） proliferation and pulmonary vascular remodeling induced by cigarette smoke exposure. A total of 24 male Wistar rats were randomly divided into 4 groups： control group （C group）, S-1M, S-3M and S-6M groups （animals in the groups were exposed to smoke for 1, 3, and 6 months, respectively）. HE staining and anti-u-smooth muscle actin antibody staining were performed to observe the degree of pulmonary vascular remodeling. Imrnunohistochemis- try and Western blotting were performed to evaluate ERK1/2 and cyclinE1 expression in pulmonary vessels. Primary cultured rat pulmonary artery smooth muscle cells （rPASMCs） were exposed to ciga- rette smoke extract （CSE）. ERK inhibitor （PD98059） and cyclinE1 siRNA were used to verify the role of ERK1/2 and cyclinE 1 in CSE-induced rPASMCs proliferation. Cell proliferation was assessed by cell counting and 5-bromo-2-deoxyuridine （BrdU） incorporation. Our results showed that abnormal pulmo- nary vascular remodeling was found in cigarette smoked rats. Compared to C group, activated ERK1/2 and cyclinE1 expression was significantly increased in smoke-exposure groups. This up-regulated ex- pression was positively correlated with the severity of pulmonary vascular remodeling, and there was positive correlation between the expression of ERK1/2 and cyclinE1. PD98059 and cyclinE1 siRNA in- hibited the proliferation of rPASMCs. The expression of cyclinE1 could be down-regulated by PD98059. Our data demonstrated that increased expression of ERK1/2 and cyclinE1 might be involved in the pathogenesis of abnormal rPASMCs proliferation and rat pulmonary vascular remodelling induced by cigarette smoke exposure.

Proteomic analysis of the serum in patients with idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension(IPAH) is a rare disease of unknown etiology.The exact pathogenesis of pulmonary arterial hypertension is still not well known.In the past decades,many protein molecules have been found to be in-volved in the development of IPAH.With proteomic techniques,profiling of human plasma proteome becomes more feasible in searching for disease-related markers.In present study,we showed the protein expression profiles of the serum of IPAH and healthy controls after depleting a few high-abundant proteins in serum.Thirteen spots had changed significantly in IPAH com-pared with healthy controls and were identified by LC-MS/MS.Alpha-1-antitrypsin and vitronectin were down-regulated in IPAH and may be valuable candidates for further explorations of their roles in the development of IPAH.

Relationship of Intracellular Free Ca^(2+) Concentration and Calcium-activated Chloride Channels of Pulmonary Artery Smooth Muscle Cells in Rats under Hypoxic Conditions

To investigate the relationship between intracellular free Ca^2＋ concentration （[Ca^2＋ ]i ） and calcium-activated chloride （Clca） channels of pulmonary artery smooth muscle cells （PASMCs） in rats under acute and chronic hypoxic conditions, acute hypoxia-induced contraction was observed in rat pulmonary artery by using routine blood vascular perfusion in vitro. The fluorescence Ca^2＋ indicator Fura-2/AM was used to observe [Ca^2＋ ]i of rat PASMCs under normal and chronic hypoxic condition. The effect of Clca channels on PASMCs proliferation was assessed by MTT assay. The Clca channel blockers niflumic acid （NFA） and indaryloxyacetic acid （IAA-94） exerted inhibitory effects on acute hypoxia-evoked contractions in the pulmonary artery. Under chronic hypoxic condition, [Ca^2＋ ]i was increased. Under normoxic condition, [Ca^2＋ If was （123.634-18.98） nmol/ L, and in hypoxic condition, [Ca^2＋]i wag （281. 754-16.48） nmol/L （P〈0. 01）. Under normoxic condition, [Ca^2＋ ]i showed no significant change and no effect on Clca channels was observed （P〉 0. 05）. Chronic hypoxia increased [Ca^2＋ ]i which opened Clca channels. The NFA and IAA-94 blocked the channels and decreased [Ca^2＋ ]i from （281.75± 16.48） nmot/L to （117.66 ±15.36） nmol/L （P〈0.01）. MTT assay showed that under chronic hypoxic condition NFA and IAA-94 decreased the value of absorbency （A value） from 0. 459±0. 058 to 0. 224±0. 025 （P〈0. 01）. Hypoxia increased [Ca^2＋ ]i which opened Cl~ channels and had a positive-feedback in [Ca^2＋ ]i. This may play an important role in hypoxic pulmonary hypertension. Under chronic hypoxic condition, Clca channel may play a part in the regulation of proliferation of PASMCs.