P2y12 Receptor Promotes Pressure Overload-Induced Cardiac Remodeling via Platelet-Driven Inflammation in Mice.

摘要: Inflammation plays a critical role in adverse cardiac remodeling and heart failure. The P2y12 receptor is one of the predominant activating receptors for platelets, thus initiating inflammatory responses under various diseases. In this study, we investigated functional significance P2y12-mediated platelet activation pressure overload-induced remodeling. Notably, knockout (P2y12-/-) mice exhibited suppressed transverse aortic constriction-induced changes hypertrophy, collagen synthesis, cell recruitment, dysfunction. Activated platelets platelet-leukocyte aggregates were markedly downregulated compared with wild-type counterparts after constriction. Moreover, bone marrow chimera experiments revealed that recipients improved function attenuated remodeling, reversed by reinjection. Platelet depletion P-selectin inhibition mimicked these protective effects limiting interaction between activated leukocytes. Furthermore, directly induced cardiomyocyte hypertrophy synthesis via α-granule exocytosis, vanished or those administered anti-NSF (N-ethlymalimide-sensitive factor) antibodies. results suggest promotes triggering series interacting leukocytes endotheliocytes.