A Natural History Study of Novel Biomarkers in Pulmonary Arterial Hypertension

肺动脉高压新型生物标志物的自然历史研究

• 批准号: 8952912
• 负责人: Michael Solomon
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8952912
• 关键词: Amendment; Biological Markers; Blood Vessels; Cardiac; Disease; Enrollment; Evolution; Genetic Predisposition to Disease; Inflammation; Injury; Institution; Institutional Review Boards; Lung; Magnetic Resonance Imaging; Measures; National Heart, Lung, and Blood Institute; Natural History; Outcome; Pathogenesis; Patients; Phenotype; Play; Process; Protocols documentation; Rare Diseases; Recruitment Activity; Resolution; Right-On; Role; Severity of illness; Site; Staging; Stimulus; United States National Institutes of Health; Vascular remodeling; Ventricular; clinically relevant; endothelial dysfunction; injury and repair; new therapeutic target; novel; prognostic; pulmonary arterial hypertension; vascular inflammation

PAH (i.e. Group 1 PAH) is a rare disorder associated with poor survival. Endothelial dysfunction resulting from 1) genetic susceptibility, and 2) a triggering stimulus that initiates pulmonary vascular injury, the two-hit hypothesis, appears to play a central role both in the pathogenesis and progression of PAH. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic PAH (IPAH) and patients with disease-associated PAH. However, despite mounting evidence of vascular inflammation in patients with PAH, detailed phenotypic studies are lacking on the temporal evolution of this process and its contribution to right ventricular (RV) and pulmonary vascular remodeling. The protocol was initially approved by the NHLBI IRB in October 2012. Subsequently IRB approval was sought and obtained at collaborating sites and various amendments were brought into alignment at all institutions by summer 2013. Referrals are being received from multiple sites. To date 51 subjects have been screened for this study and 14 have been enrolled. We hypothesize that a detailed characterization of the temporal evolution of vascular inflammation and neurohormonal activation in PAH and its impact on RV and pulmonary vascular function will add prognostic value to traditional measures of disease severity and suggest novel therapeutic targets for future research.

PAH（即1组PAH）是一种与存活不良有关的罕见疾病。 由1）遗传敏感性引起的内皮功能障碍，以及2）引发肺血管损伤的触发刺激，两次打击的假设似乎在PAH的发病机理和进展中起着核心作用。 炎症似乎会促进这种功能失调的内皮表型，从而传播了特发性PAH（IPAH）的遗传易感患者的损伤和修复周期和与疾病相关的PAH患者。 然而，尽管PAH患者的血管炎症有越来越多的证据，但该过程的时间演变及其对右心（RV）和肺血管重塑的贡献缺乏详细的表型研究。 该协议最初是由NHLBI IRB于2012年10月批准的。随后在协作地点寻求IRB批准并获得了IRB批准，并于2013年夏季在所有机构中对所有机构进行了对齐。将从多个地点收到推荐。 迄今为止，已经筛选了51名本研究的受试者，并已入学14名。 我们假设对PAH中血管炎症和神经激活的时间演变的详细表征及其对RV和肺血管功能的影响将为疾病严重程度的传统指标增加预后价值，并建议对未来研究的新型治疗靶标。