Pulmonary arterial hypertension (PAH) is a fatal and complex disease characterized by multifactorial involvement in pulmonary vascular remodeling, leading to heart failure. It is difficult to treat and has a poor long-term prognosis. Recent studies highlight the significant role of epigenetic modulation in the pathophysiological progression of PAH, offering new therapeutic approaches to improve clinical outcomes. This article summarizes the role of epigenetic modulation in the development and progression of PAH, focusing on deoxyribonucleic acid methylation, ribonucleic acid methylation, histone modifications, and non-coding ribonucleic acid, in order to understand the role of epigenetic modulation in PAH and identifying new evaluation indexes and therapeutic targets, thereby improving the prognosis of PAH.
Pulmonary arterial hypertension(PAH) is a kind of pulmonary hypertension disease. Recently, the researches of its pathogenesis have reached more and more deeply. The treatment of pulmonary arterial hypertension is individual and systematic, not only relying on medicine treatment. The treatment of PAH is as follows: common treatment, non-specific medicine treatment, targeted medicine treatment, NO breath-in treatment, gene treatment, intervention and surgery treatment.The article reviews the main treatment of pulmanory arteral hypertesion to provide new thought and evidence in clinic.
Pulmonary arterial hypertension (PAH) is a severe, progressive disease leading to right ventricular failure and finally death. Lung transplantation is recommended for PAH patients who do not respond to targeted drug combination therapy or World Health Organization functional class (WHO FC) Ⅲ or Ⅳ. However, only 3% of PAH patients can recieve the lung transplantation. A novel implantable interatrial shunt device (ISD) can create a relatively fixed right-to-left shunt established by balloon atrial septostomy (BAS). The device may decompress the right sided chambers, facilitate left heart filling, improve organ perfusion and reduce the likelihood of syncope, acute pulmonary hypertensive crisis and death. The systemic oxygen transport improves despite hypoxemia. Implantation is simple, feasible and safe, and the X-ray time and operation time are short. There is no severe complication or thrombosis during the mid-term follow-up of the clinical studies and the device remained patent. The syncope symptoms, six-minute walk distance, cardiac index and systemic oxygen transport improve significantly in the patients. ISD may be currently the last alternative treatment to improve symptoms and prolong survival in currently drug-resistant patients with severe PAH.
ObjectiveTo enhance the understanding of Takayasu’s arteritis (TA) with pulmonary vascular involvement through the analyses on clinical features.MethodsA retrospective study was conducted to analyze the clinical records of patients diagnosed as TA with pulmonary vascular involvement admitted to Beijing Anzhen Hospital from January 2007 to August 2017.ResultsIn recent 10 years, there were 233 patients diagnosed as TA in Beijing Anzhen Hospital, 17 of them were involved with pulmonary arterial, which accounted for 7.3%. Fourteen patients were females, 3 patients were males. The age ranged from 16 to 59 years with an average of (40±13) years. Among the 17 patients, dyspnea (15 cases, 88.2%) was the most common symptom, and unequal blood pressure of upper limbs (9 cases, 52.9%) was the main sign. Thirteen patients had pulmonary hypertension by echocardiographic examination. Angiographic data showed that multi-lobular and multi-segmental pulmonary branches were predominantly affected. Unilateral involvement of pulmonary artery was more common than bilateral involvement, while the right pulmonary arteries were more often affected than the left. Thirteen patients received hormone and immunosuppressive therapy, 11 patients received anticoagulation or antiplatelet therapy, and 5 patients received targeted treatment of pulmonary artery pressure.ConclusionsThe clinical manifestation of TA is unspecific and misdiagnosis rate is relatively high. Improving the understanding of TA is necessary so as to reduce the misdiagnosis rate at an early stage and ameliorate the prognosis.
ObjectiveTo analyze perioperative prognostic factors of pediatric patients undergoing surgical correction of ventricular septal defect (VSD)and severe pulmonary arterial hypertension (PAH). MethodsForty pediatric patients with VSD and severe PAH (mean pulmonary artery pressure (PAPm) < 50 mm Hg)who underwent surgical repair in Beijing Anzhen Hospital from 2004 to 2012 were included in the study. There were 21 male and 19 female patients with their age of 7.2±3.3 years and body weight of 19.6±7.1 kg. All the patients were randomly divided into 2 groups:Group Ⅰ (Group=0, n=20, M/F:12/8, continuous nitroglycerin administration via central venous catheter (CVC)and GroupⅡ (Group=1, n=20, M/F:9/11, continuous prostaglandin E1 (PGE1)administration via CVC). The duration of intubation (Tintubation)was used as the dependent variable (Y). Patient age, cardiopulmonary bypass time (TCPB), postoperative PAPm, pulmonary vascular resistance index (PVRI), systemic to pulmonary pressure ratio (Ps/p), Group, left ventricular stroke work index (LVSWI)and right ventricular stroke work index (RVSWI)were used as independent variables (X). Multivariate liner regression analysis model was used to evaluate the influence of X on Y. ResultsThere was no perioperative death or severe complication in this group. Perioperative prognostic factors of pediatric patients undergoing surgical correction of VSD and severe PAH included group[x1, P=0.004, 95% CI (-71, -16)], TCPB[x2, P=0.011, 95% CI (0.9, 5.8)], posto-perative PAPm (x3, P=0.004 with 95% CI 3.2 to 13.3), RVSWI (x4, P=0.003 with 95% CI-16.9 to-4.3)and PVRI (x5, P=0.03 with 95% CI-0.29 to-0.02). The standardized regression equation was:Y=-0.60x1+0.54x2+2.22x3-1.70x4-0.15x5. ConclusionPGE1 administration, TCPB, postoperative PAPm, RVSWI and PVRI are predominant perioperative prognostic factors of pediatric patients undergoing surgical correction of VSD and severe PAH.
Objective To explore the clinical effect and safety of sildenafil combined with bosentan in the treatment of connective tissue disease associated moderate-severe pulmonary arterial hypertension (CTD-MS-PAH ). Methods Seventy-six patients with CTD-MS-PAH during January 2013 to January 2017 were collected and divided into group A (41 cases) and group B (35 cases) using a stratified random sampling approach. The patients in group A received 25 mg sildenafil tablet therapy, three times a day. The patients group B received 25 mg sildenafil and 62.5 mg bosentan tablet therapy, twice a day. Both groups were treated for 12 weeks. Before and after the trial, all patients undertook six-minute walk test. Meanwhile the Borg dyspnea index score, the pulmonary artery systolic pressure (PASP), right ventricular diameter (RVD), B-type natriuretic peptide (BNP), the partial pressure of oxygen in artery (PaO2), blood pressure, heart rate, liver and kidney function were all measured. Results After the therapy, six-minute walking distance increased, Borg dyspnea index score decreased, PASP, RVD and plasma BNP decreased, and PaO2 increased in both groups (all P<0.05), but group B was superior to group A (allP<0.05). There were no significant differences in blood pressure, heart rate, liver or kidney function compared with those before the treatment in both groups (allP>0.05). Conclusion Sildenafil combined with bosentan can significantly decrease the level of pulmonary arterial pressure and effectively improve the cardiopulmonary function in CTD-MS-PAH patients with good safety.
ObjectiveTo systematically review the efficacy and safety of treprostinil for patients with pulmonary arterial hypertension (PAH). MethodDatabases including PubMed, EMbase, The Cochrane Library (Issue 2, 2015) , WanFang Data, CBM and CNKI were searched to collect randomized controlled trials (RCTs) about treprostinil for PAH from inception to 1st May 2015. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsA total of seven RCTs including 1 662 participants were finally included. The results of meta-analysis showed that, compared with placebo, treprostinil could increase patients' 6-min walk distance (MD=19.62, 95%CI 0.55 to 38.69, P=0.63) , reduce Brog score (MD=-0.52, 95%CI -0.96 to -0.07, P=0.06) , decrease pulmonary vascular resistance (MD=-3.23, 95%CI -4.80 to -1.66, P=0.42) and improve cardiac index (MD=0.19, 95%CI 0.08 to 0.30, P=0.44) , but there were no significant differences between two groups in incidence of mortality (OR=0.84, 95%CI 0.47 to 1.50, P=0.82) and clinical deterioration (OR=0.84, 95%CI 0.56 to 1.26, P=0.95) . ConclusionsCurrent evidence reveals that treprostinil can improve excise capacity, respiratory function and ameliorate hemodynamic index, but can't reduce the incidence of mortality and clinical deterioration in patients with PAH.
ObjectiveTo observe the pathological changes in heart and lung tissues in rats with pulmonary hypertension induced by monocrotaline. MethodsTwenty-four male Sprague-Dawley rats were randomly and equally divided into an experimental group and a control group. The rats in the experimental group were intraperitoneally injected with monocrotaline to induce pulmonary hypertension, and the rats in the control group were treated with saline. All rats were fed for 3 weeks, and the general situation were observed. Then the rats were sacrificed for measurement of mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index [RV/(LV+S)], changes of myocardial cells and lung vascular, calculated density of middle membrane smooth muscle cells (SMC) in medium/small pulmonary arteries accompanied with bronchi and alveoli, media thickness of pulmonary artery (PAMT), the percentage of wall thickness with outer diameter (WT%), the percentage of wall area with total area (WA%), the average diameter of myocardial cells (AD), and myocardial nuclei density (MND). ResultsCompared with the control group, the condition of rats in the experimental group were getting worse obviously.mPAP and RV/(LV+S) were both increased (both P < 0.05). The observation by light microscope revealed that obvious myocardial hypertrophy and structure disturbances, severe luminal stenosis of medium/small pulmonary arteries, medial thickening, infiltration of inflammatory cell in tissue space, proliferation of unorganized collagen fibers in the experimental group. The observation by electronic microscope showed proliferation of endothelial cell with irregular nuclei, increased organelles and vacuoles in the experimental group. The differences in SMC, PAMT, WT%, WA%, AD, and MND were significant between two groups (all P < 0.05). ConclusionsThe monocrotaline can induced pulmonary hypertension and right ventricular hypertrophy. The mechanism may be related to severe stenosis or occlusion of the vessel lumen caused by plexiform proliferation of endothelial cells, proliferation of smooth muscle cells and collagen fibers, compensatory hypertrophy and hyperplasia of myocardial cells.
【摘要】 目的 探讨肺动脉高压患者药物靶向治疗的效果与耐受性。 方法 回顾分析2008年1月〖CD3/5〗2009年8月期间8例肺动脉高压患者分别接受波生坦及西地那非治疗的临床资料,评估其临床表现、WHO肺动脉高压功能分级、6 min步行距离及肺动脉收缩压在基线及治疗3个月后的变化。 结果 治疗后3个月,患者均能耐受药物治疗,无严重不良反应发生。WHO肺动脉高压功能分级在治疗前平均(31±04),治疗后为(23±09),明显得到改善(Plt;005)。肺动脉收缩压在治疗前平均(695±112 ) mm Hg(1 mm Hg=0133 kPa),治疗后为(483±124) mm Hg,明显降低(Plt;005)。6 min步行距离在治疗前平均(324±48) m,治疗后为(400±43) m,明显延长(Plt;005)。 结论 肺动脉高压患者药物靶向治疗的疗效显著,且耐受良好。【Abstract】 Objective To examine the effects of target medical therapy in patients with pulmonary arterial hypertension(PAH). Methods To determine the safety and efficacy of bosentan and sildenafil in eight patients with PAH.The patients’ clinical features, six minutes walking diastance, WHO functional class and systolic pulmonary arterial pressure (SPAP) were measured at baseline and at three months after initiating target medial treatment. Results At the three months followup assessments, WHO functional class was improved with 31±04 vs 23±09 (Plt;005); SPAP was significantly decreased with(695±112 ) mm Hg vs (483±124) mm Hg (Plt;005), the six minutes walking distance was significantly increased with(324±48) m vs(400±43) m (Plt;005). Target medical treatment was well tolerated. Conclusion Target medical treatment is well tolerated and has beneficial effects on PAH.
ObjectiveTo systematically review the efficacy and safety of prostacyclin for patients with pulmonary arterial hypertension (PAH).MethodsWe searched PubMed, EMbase, The Cochrane Library, WanFang Data, CBM and CNKI databases for randomized controlled trials (RCTs) compared prostacyclin with placebo from inception to April 2018. Two reviewers independently screened literature, extracted the data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.3 software.ResultsEleven RCTs including 2 549 participants were included. The results of meta-analysis showed that, compared with placebo group, prostacyclin group was superior to the placebo group in 6-min walk distance (MD=31.10, 95%CI 16.89 to 45.30, P<0.001), mortality (RR=0.62, 95%CI 0.41 to 0.94,P=0.03), Brog score (MD=–0.88, 95%CI –1.28 to –0.49, P<0.001), mean pulmonary arterial pressure (MD=–3.31, 95%CI –4.34 to –2.29,P<0.001) and cardiac index (MD=0.32, 95%CI 0.14 to 0.51,P<0.001). However, there were no differences between two groups in reducing delaying time to clinical deterioration (RR=1.27, 95%CI 0.99 to 1.63,P=0.06), tolerability (RR=0.74, 95%CI 0.42 to 1.31, P=0.30) and pulmonary vascular resistance (MD=–4.35, 95%CI –8.85 to 0.15, P=0.06).ConclusionsCurrent evidence reveals that prostacyclin therapy appears to be superior to the placebo in reducing the mortality, improving excise capacity, respiratory and cardiac function, and ameliorating mean pulmonary arterial pressure for pulmonary arterial hypertension. However, the efficacy of prostacyclin in delaying time to clinical deterioration, tolerability and pulmonary vascular resistance for PAH is not clear. Due to the limited quality and quantity of included studies, more high quality RCTs are required for further verification.