GP130 Antagonism in Porcine RV Pressure Overload

项目摘要 肺动脉高压(PAH)是一种致命性疾病，中位生存期仅为5-7年。 在病理生理学上，PAH是一种进行性毛细血管前血管病变，它增加了 在降低肺动脉顺应性的同时降低肺动脉压和肺血管阻力。 肺血管的变化增加了右心室的工作负荷，最终导致 右室功能不全(RVD)。RVD的存在是PAH死亡的最大危险因素； 然而，目前还没有直接针对RV的PAH疗法。在这项建议中，我们将调查 右室心肌细胞gp130激活通过微管促进心肌细胞功能障碍的假说 导致T管排列紊乱和线粒体代谢功能障碍的重塑。我们将使用国家- 探讨gp130拮抗对右室的分子和生理影响的最新方法 猪右室衰竭时的心功能。

Project Summary Pulmonary arterial hypertension (PAH) is a lethal disease with a median survival of only 5-7 years. Pathophysiologically, PAH is a progressive vasculopathy of the precapillary pulmonary vessels that increases pulmonary arterial pressures and pulmonary vascular resistance while reducing pulmonary arterial compliance. The changes in the pulmonary vasculature augment the work load of the right ventricle, which ultimately results in right ventricular dysfunction (RVD). The presence of RVD is the greatest risk factor for death in PAH; however, no current PAH therapies actually target the RV directly. In this proposal, we will investigate the hypothesis that GP130 activation in RV cardiomyocytes promotes cardiomyocyte dysfunction via microtubule remodeling which causes t-tubule derangements and mitochondrial metabolic dysfunction. We will use state- of-the-art approaches to probe the molecular and physiological effects of GP130 antagonism on right ventricular function in porcine RV failure.