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 （PASMC）远端延伸、SMC对凋亡的抵抗、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）是在多种形式的肺动脉高压（PAH）中发生突变或功能失调的生长控制受体。先前，我们在人PASMC （HPASMC）中证明转录因子过氧化物酶体增殖物激活受体（PPARgamma）被BMPR2激活，并诱导ApoE。在第一个资助期（HA4348/2-1），我们发现PPARgamma是脂质和葡萄糖代谢的中心调节因子，是血管SMC中BMP2和tgf - β1通路之间缺失的一环，可以保护PAH。

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.