PPARgamma Regulation In Pulmonary Vascular Disease - Beneficial Effects on Pulmonary Arterial Smooth Muscle Cells

肺动脉高压血管疾病在很大程度上与生长因子介导的平滑肌细胞(SMC)增殖增加、肺动脉SMC远端延伸(PASMC)、SMC抗凋亡、内皮功能障碍和炎症(血管收缩的贡献较小)有关。骨形态发生蛋白受体2(BMPR2)是一种生长控制受体，在许多形式的肺动脉高压(PAH)中发生突变或功能障碍。以前，我们在人PASMC(HPASMC)中证明了转录因子过氧化体增殖物激活受体(PPARGamma)被BMPR2激活并诱导ApoE。在第一个资助期(HA4348/2-1)，我们发现PPAR-伽马，一种脂和糖代谢的中央调节因子，是血管平滑肌细胞中BMP2和转化生长因子β-1通路之间缺失的一环，从而保护血管免受PAH的影响。

Pulmonary hypertensive vascular disease relates in large part to increased growth factor-mediated smooth muscle cell (SMC) proliferation, distal extension of pulmonary arterial SMC (PASMC), SMC resistance to apoptosis, endothelial dysfunction and inflammation (with a smaller contribution from vasoconstriction). Bone morphogenetic protein receptor 2 (BMPR2) is the growth-controlling receptor that is mutated or dysfunctional in many forms of pulmonary arterial hypertension (PAH). Previously, we demonstrated in human PASMC (HPASMC) that the transcription factor peroxisome proliferator-activated receptor (PPARgamma) is activated by BMPR2, and induces ApoE. In the first funding period (HA4348/2-1), we identified PPARgamma, a central regulator of lipid and glucose metabolism, as a missing link between BMP2 and TGFβ1 pathways in vascular SMC, that protects from PAH.