Weekly Virtual CVI Frontiers in Cardiovascular Science Seminar

Stanford Cardiovascular Institute are organizing weekly virtual CVI Frontiers in Cardiovascular Science Seminar. The Zoom webinars are open to the public. We encourage you to attend and have a lively Q&A discussion.

Below are the Zoom details for our upcoming speaker.

Speaker: Joan Heller Brown, PhD, Distinguished Professor and Chair, Department of Pharmacology, UCSD School of Medicine.

Talk Title: Igniting the Flame of Inflammation through Cardiomyocyte CAMKII and Inflammasome Activation.

Abstract: Inflammation is associated with cardiac remodeling and heart failure, but how it is triggered in response to non-ischemic interventions is not known. Using cardiac specific CaMKIIδ KO mice (CKO) we show that angiotensin II infusion or transverse aortic constriction (TAC) induce rapid and robust increases in pro- inflammatory chemokine and cytokine gene expression resulting from activation of CaMKII and NFkB.. Priming and activation of the NLRP3 inflammasome, are also increased through cardiomyocyte CaMKII. Cardiomyocytes isolated at 3 days TAC exhibit increased inflammatory gene mRNA and inflammasome activation while the non-cardiomyocyte compartment does not. Systemic inflammation and endothelial cell activation are also increased by TAC, and diminished in CKO mice. Macrophages accumulate in the heart by 2 weeks TAC and this response is diminished in CKO and by blocking MCP-1 or inflammasome activation. Cardiac fibrosis is also decreased by these interventions. Subsequent development of ventricular dysfunction is attenuated in the CKO and by inhibition of NFkB or inflammasome signaling within the first 2 weeks after TAC. We conclude that CaMKIIδ signaling within cardiomyocytes transduces hormonal and other non-ischemic signals to initiate inflammatory responses, which then drive subsequent systemic inflammation, immune cell recruitment, fibrosis and adverse remodeling.