Inflammation and NLRP3 Inflammasome Activation Initiated in Response to Pressure Overload by CaMKIIδ Signaling in Cardiomyocytes are Essential for Adverse Cardiac Remodeling

Background: Inflammation is associated with cardiac remodeling and heart failure, but how it is initiated in response to non-ischemic interventions in the absence of cell death is not known. We tested the hypothesis that activation of CaMKIIδ in cardiomyocytes in response to pressure overload elicits inflammatory responses leading to adverse remodeling. Methods: Mice in which CaMKIIδ was selectively deleted from cardiomyocytes (CMs) (Cardiac specific knockout; CKO) and floxed control (CTL) mice were subjected to transverse aortic constriction (TAC). The effects of CM-specific CaMKIIδ deletion on inflammatory gene expression, inflammasome activation, macrophage accumulation and fibrosis were assessed by qPCR and histochemistry and ventricular remodeling by echocardiography. Results: TAC induced increases in cardiac mRNA levels for pro-inflammatory chemokines and cytokines within 3 days and these responses were significantly blunted when cardiomyocyte CaMKIIδ was deleted. Apoptotic and necrotic cell death w...