干预交感神经治疗肺动脉高压的研究进展

肺动脉高压(PAH)是以肺动脉平滑肌细胞增生和肺中小动脉重构为主要特征,导致肺血管阻力进行性增加,最终引起右心室肥厚和右心衰竭的一种致死性疾病。越来越多的研究显示,交感神经在PAH患者中的交感活性增强,且PAH患者的生存率和预后与交感神经活性密切相关。交感神经系统的激活在肺动脉重塑中发挥重要作用。目前干预交感神经系统治疗PAH的手段包括α/β受体阻滞剂、血管紧张素转换酶(ACE)抑制剂、血管紧张素1型受体(AT1R)抑制剂、醛固酮受体拮抗剂、ACE2激动剂、肺动脉去神经支配、肾交感消融和交感神经节阻滞等,均显示出一定的心脏和代谢保护作用,改善了心肺血流动力学。本文将对干预交感神经系统治疗PAH的相关基础及研究进展进行综述。     

肺动脉平滑肌细胞:肺动脉高压的关键治疗靶点

肺动脉高压(PAH)是一种进展快、预后欠佳、死亡率高的心血管疾病。研究表明,肺血管重构是PAH发生发展的重要病理基础,而肺动脉平滑肌细胞的增殖和肥大是PAH肺血管重构的主要病理改变。在PAH时,肺血管平滑肌细胞由收缩表型向增殖状态的合成表型转化,主要表现为肺血管平滑肌细胞的增殖和肥大。上述病理改变最终导致肺血管管腔狭窄,管壁僵硬,进而促进PAH的发生发展。本文对肺动脉平滑肌细胞在PAH中的关键作用及作用机制进行阐述,为临床防治PAH提供新靶点和新策略。     

心血管磁共振在评价肺动脉高压患者右心功能中的应用

肺动脉高压(pulmonary arterial hypertenaion,PAH)是一种以小肺动脉血管重构为特征的肺血管疾病[1],肺血管阻力往往进行性升高,最终导致右心室功能衰竭甚至死亡.准确评价右心室功能对明确PAH病情严重程度,评价疗效和判断预后具有非常重要的意义.     

干细胞移植治疗肺动脉高压研究进展

肺动脉高压(Pulmonary arterial hypertension,PAH)是一种以肺动脉血管重构为特征,导致肺血管阻力升高和右心室功能障碍的进行性疾病。目前针对PAH的治疗只能暂缓患者病情,不能有效治疗。近年来,干细胞治疗肺动脉高压受到了许多关注,本文就目前干细胞治疗PAH的进展进行综述。     

肺动脉高压治疗新方法——内皮素受体A治疗性疫苗

肺动脉高压(PAH)是一种慢性致死性疾病,现有针对PAH的药物虽有一定的治疗效果,但其预后仍不尽人意,需要探索新的治疗方法。治疗性疫苗是治疗PAH的新方法。内皮素(ET)系统,尤其是ET-1和内皮素受体A(ETAR)的异常激活与PAH的发病机制密切相关,ETAR是PAH治疗性疫苗的理想靶点。我们最近成功研发出一种以ETAR为靶点的PAH治疗性疫苗ETRQβ-002。该疫苗能显著降低两种PAH动物模型的肺动脉压,改善甚至逆转肺小动脉重构和右心室肥厚,且没有发现明显的靶器官免疫损害和肝肾功能异常,说明ETRQβ-002是一种能有效并且安全地治疗PAH的治疗性疫苗。     

血管重构在动脉型肺动脉高压中的研究进展

动脉型肺动脉高压（PAH）是以肺动脉压力持续升高、肺小动脉结构持续改变为特征的致命性疾病,肺动脉重构是其主要的病理学特点。许多研究发现PAH中血管重构的病理机制主要包括各种细胞的病理学改变和多种分子信号通路的参与,最新的研究指出表观遗传学也参与血管重构,从而导致疾病的发生发展。目前针对PAH发病机制的各种新型药物及新疗法正在被开发,其副作用更小、疗效更佳。本文重点阐述PAH中血管重构的病理机制包括病理学改变、新分子信号通路及表观遗传学内容,以及治疗的新进展。     

肺动脉高压药物治疗的新进展

肺动脉高压(pulmonary arterial hypertension,PAH)是一种渐进性疾病,其特点为肺血管重塑,导致肺动脉压增高和右心室衰竭。近年来随着人们对 PAH 发病机制认识地不断提高,针对 PAH发病各环节的治疗均取得了长足进展,从而改变了 PAH 患者的命运。     

中医药治疗肺动脉高压的研究进展

肺动脉高压(PAH)属于典型的慢性严重心肺疾病,其主要病理特征是肺血管结构和功能异常,进而导致肺动脉管腔进行性狭窄、闭塞,肺血管阻力不断升高,最终导致患者出现右心衰竭.目前,靶向药物可以改善PAH患者的生活质量,但长期疗效和预后仍不佳.近年随着诊断水平的提高,越来越多的PAH患者得到诊断,而通过中医药干预PAH也成为研...     

肺动脉高压的研究现状

肺动脉高压（PAH）是不同病因导致的、以肺动脉压力和肺血管阻力升高为特点的一组病理生理综合征，主要病理机制是血管收缩、血管重构和原位血栓形成，最终导致右心负荷增加，右心功能衰竭（心衰）。近年，PAH的研究包括定义、分类、发病机制、诊断和治疗等方面均取得了重大突破，本文重点介绍PAH发病机制和治疗。     

肺血管重构与磷酸二酯酶关系的新进展

肺动脉高压（pulmonary artery hypertension, PAH）是一大类以肺动脉压和肺循环阻力升高为特征的严重疾病。根据发病诱因可分为特发性PAH、家族性PAH、缺氧性PAH及结缔组织病引起的PAH;感染因素如艾滋病等引起的PAH;以及因先天性心脏病左向右分流引起的PAH;急、慢性肺动脉栓塞引起的PAH等。各类PAH的发病机制大部分未明,但其共同特征是肺动脉压及肺血管阻力升高、右心室后负荷增加,从而导致右心衰竭甚至死亡。不同发病原因的PAH进展过程中,都会出现肺血管收缩和肺血管重构相同的病理学特征。     

肺动脉高压治疗的最新进展

肺动脉高压是各种原因引起的肺动脉压力持续升高的临床综合征.若缺乏相应的治疗,将导致肺血管重塑,最终发展为右心衰竭,预后极差.但早期诊断及合理治疗可提高该病患者的生存率并改善患者的生存质量.近年,对肺动脉高压发病机制认识的不断深入推动了肺动脉高压治疗手段的发展,现将肺动脉高压治疗的最新进展综述如下.     

电压依赖性钾离子通道在肺动脉高压发病过程中的作用

肺动脉高压是一种肺血流受限引起肺血管阻力和压力持续性增高,最终导致右心衰竭甚至死亡的综合征.病理生理学改变主要为肺血管收缩、重塑及原位血栓形成.研究表明,钾离子通道尤其电压依赖性钾离子通道功能与表达水平的降低是引起肺血管平滑肌细胞增殖和凋亡异常、肺血管重塑的关键因素.本文着重论述近年来有关电压依赖性钾离子通道与肺动脉高...     

人源性脐带间充质干细胞治疗实验性肺动脉高压所致右心衰竭的疗效观察

目的 拟通过建立MCT诱导的PAH大鼠模型,观察人脐带间充质干细胞（UC-MSCs）干预对大鼠PAH和右心衰竭的治疗效应。方法 实验动物分为3组（空白对照组、PAH组和UC-MSCs组）,在MCT腹腔注射1周后进行干预,UC-MSCs组舌下静脉注射UC-MSCs悬液,空白对照组和PAH组舌下静脉注射等量生理盐水。第4周大鼠行右心超声心动图、右心导管测压、右心肥厚指数以及肺组织病理等检测。结果 与对照组相比,PAH组大鼠右心室游离壁厚度(RVWT)和右心室内径(RVID)显著增大,肺动脉血流加速时间与射血时间比值（PAT/PET）显著下降,右心收缩压（RVSP）和右心肥厚指数(RVHI)显著增高,肺小动脉血管壁厚度（WT）明显增厚。与PAH组相比,UC-MSCs组RVWT和RVID显著减小,PAT/PET明显升高,RVSP和RVHI明显降低,WT明显变薄。结论 利用MCT腹腔注射成功制备PAH大鼠模型,经舌下静脉注射UC-MSCs可以显著降低肺动脉压力,改善右心功能,逆转肺血管重构。     

Pulmonary arterial hypertension and women

Pulmonary arterial hypertension (PAH) is a progressive disorder with a poor prognosis. It is characterized by sustained elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). It is defined hemodynamically by a mean PAP over 25 mm Hg, a pulmonary arterial wedge pressure of 15 mm Hg or less (which excludes left sided lesions), and a PVR of 3 or more Wood units (240 dyn.sec.cm-5). Patients are limited by exertional dyspnea, pre- or true syncope, chest pain, and edema/ascites when right heart failure supervenes. PAH afflicts predominantly young women and the diagnosis is often delayed. Three processes contribute to progressive arterial narrowing: vasoconstriction, vascular remodeling, and thrombosis in situ. The diagnosis of PAH must be confirmed and its etiology must be identified before appropriate therapy can be instituted. Right heart catheterization is necessary to establish the diagnosis, severity, and prognosis of PAH and to ascertain its etiology and to evaluate vasoreactivity, which guides therapy. Treatment of PAH includes vasodilators, supplemental O2, anticoagulation, diuretics, digoxin, intravenous inotropic therapy for decompensated right ventricular failure, and lung or combined heart-lung transplantation for those patients who continue to deteriorate with a poor quality of life despite pharmacologic therapy. Calcium channel blockers are beneficial in a small minority of patients. Prospective, controlled, randomized trials of approved vasodilator agents have enrolled a large proportion of women (70-85%). Agents such as the endothelin-1 receptor antagonist bosentan, the phosphodiesterase-5 inhibitor sildenafil, and the prostanoids have been shown to improve symptoms, exercise capacity, and, in most instances, delay clinical worsening. The clinical outcomes of patients with PAH have improved with the judicious use of contemporary therapies.     

YC-1 attenuates hypoxia-induced pulmonary arterial hypertension in mice

BackgroundPulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance and elevation of pulmonary arterial pressure, leading to right ventricular failure and eventual death. Currently, no curative therapy for PAH is available, and the overall prognosis is very poor. Recently, direct activators of soluble guanylyl cyclase (sGC) have been tested as a novel therapeutic modality in experimental models of pulmonary arterial hypertension (PAH).ObjectiveIn this study, we used in vitro and in vivo models to evaluate the therapeutic potential of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), a dual functioning chemical, as a direct activator of guanylyl cyclase and an inhibitor of hypoxia-inducible factor-1.MethodsWe analyzed the effects of YC-1 on cell proliferation and the levels of p21 and p53 in human pulmonary artery smooth muscle cells (HPASMCs) under hypoxia. We also determined the effects of YC-1 on expression of endothelin-1 (ET-1) and phosphorylation status of endothelial nitric oxide synthase (eNOS) at Ser¹¹⁷⁹ in human pulmonary artery endothelial cells (HPAECs) under hypoxia. In mice, hypoxic PAH was induced by exposure to normobaric hypoxic conditions for 28 days. To assess preventive or therapeutic effects, randomized mice were subjected to once daily i.p. injections of YC-1 for the entire hypoxic period (5 mg/kg) or for the last seven days of a 28-day hypoxic period (5 and 10 mg/kg). On day 28, we measured the right ventricular systolic pressure (RVSP) and determined the degrees of right ventricular hypertrophy (RVH) and vascular remodeling.ResultsIn HPASMCs, YC-1 inhibited hypoxia-induced proliferation and induction of p53 and p21 in a concentration-dependent manner. Also, YC-1 suppressed the hypoxia-induced expression of ET-1 mRNA and dephosphorylation of eNOS at Ser¹¹⁷⁹ in HPAECs. In the preventive in vivo model, a daily dose of 5 mg/kg YC-1 significantly prevented the elevation of RVSP, development of RVH, and pulmonary vascular remodeling, which were caused by hypoxic exposure. In the therapeutic model, YC-1 at daily doses of 5 and 10 mg/kg alleviated RVH and pulmonary vascular remodeling but did not prevent the elevation of RVSP.ConclusionsOur results indicate that YC-1 prevents the development of hypoxia-induced PAH in a preventive model and alleviates RVH and pulmonary vascular remodeling in a therapeutic model. Therefore, these data imply that YC-1 has therapeutic potential for use in a single or combination therapy for PAH.     

微小RNA在肺动脉高压发病机制中的研究进展

肺动脉高压是一种致命性疾病,缺氧、炎症、遗传等各种病因导致肺血管重塑、肺动脉压力升高,最终导致右心衰竭,甚至死亡.但目前对肺动脉高压的发病机制并不清楚,尚无治愈肺动脉高压的药物.近年来,微小RNA在许多疾病病理和生理过程中发挥的作用引起了人们的关注,许多研究表明微小RNA有逆转肺血管重塑,从而治愈肺动脉高压的可能.本文就研究较多的微小RNA在肺动脉高压的发病机制,尤其是参与血管重塑的几条通路的研究进展作一综述.     

Novel Treatment Pathways in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a severe and progressive vascular disease characterized by pulmonary vascular remodeling, proliferation, and inflammation. Despite the availability of effective treatments, PAH may culminate in right ventricular failure and death. Currently approved medications act through three well-characterized pathways: the nitric oxide, endothelin, and prostacyclin pathways. Ongoing research efforts continue to expand our understanding of the molecular pathogenesis of this complex and multifactorial disease. Based on recent discoveries in the pathobiology of PAH, several new treatments are being developed and tested with the goal of modifying the disease process and ultimately improving the long-term prognosis.     

Exercise physiology and pulmonary arterial hypertension

The lungs are the only organ that receives the entire cardiac output with every stroke. The pulmonary circulation is normally a high-flow, low-resistance, low-pressure system that carries blood into the pulmonary microcirculation. In pulmonary artery hypertension (PAH)vascular remodeling contributes to a sustained elevation of pulmonary vascular resistance (PVR) and pulmonary artery pressure (PAP) as a result of vascular remodeling characterized largely by vascular smooth muscle cell proliferation and medial hypertrophy, and endothelial cell proliferation resulting in lumen obliteration. The loss of pulmonary arterial compliance and development of elevated PVR puts an excessive burden on the right ventricle due to the increased workload necessary to overcome the downstream pressure, ultimately leading to right-sided heart failure. The functional status of the pulmonary circulation and the levels of PVR and PAP ultimately determine the outcome of patients with PAH. Study of the pressure–flow relationships in the pulmonary vascular bed will provide an improved appreciation of the pathophysiology of pulmonary hypertension.     

白细胞介素-6与低氧性肺动脉高压关系的探究

肺动脉高压（PAH）是一种常见的临床症状,凡是能引起血管阻力增大、血流量增多的因素都可成为其诱因。低氧性肺动脉高压（HPH）则是以低氧性肺动脉收缩和低氧性肺血管重构引起的肺动脉压持续升高为特征的病症。急、慢性低氧均可引起白细胞介素-6（IL-6）的分泌,导致炎症细胞浸润,继而通过对动脉内膜的改建引起PAH。