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

• Applicant: Professor Dr. Georg Hansmann
• Subject Area: Pediatric and Adolescent Medicine ; Cardiology, Angiology
• Term: since 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251767846

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.

• DFG Programme: Research Grants
• International Connection: France, USA
• Co-Investigators: Professor Philippe Boucher, Ph.D.; Professor Dr. Daniel Greif; Professor Dr. Danny David Jonigk