Cardiac sympathetic afferent denervation reduces matrix metalloproteinase expression and improves cardiac remodeling in rats post myocardial infarction

Abstract In a previous study from our laboratory, we demonstrated that chronic and selective cardiac sympathetic afferent (spinal) denervation at the time of myocardial infarction (MI) using epicardial application resiniferatoxin (RTX), neuronal toxin capable inducing rapid degeneration transient receptor potential vanilloid 1 (TRPV1)-expressing neurons fibers, markedly reduced remodeling process 9–11 weeks post-MI in rats. This included hypertrophy, fibrosis apoptosis. Here, further investigated effect RTX MI on extracellular matrix (ECM) post-MI. Echocardiographic morphologic data that, compared to MI+vehicle, MI+RTX exhibited significantly slower LV chamber dilation (6-week echocardiographic data: left ventricular end-diastolic diameter, 10.7±0.2 vs. 9.6±0.3 mm; end-systolic diameter: 8.8±0.2 7.8±0.3 MI+vehicle MI+RTX, n=18, p<0.05; mean±SE). Scanning electron microscopy showed collagen deposition peri-infarct area Western blot zymography were used evaluate metalloproteinase (MMP) expression activity, which is responsible for degrading ECM contributing post MI. Our suggest time-dependent increases MMP infarcted hearts largely prevented increase MMP9 but not MMP2, 4 both increased MMP2 activities myocardium 8–10 We MI-induced inflammation, has been reported as an upstream mechanism triggering activation The show abolished plasma extravasation macrophage infiltration cytokine content or remote These exerts local anti-inflammatory reduces by preventing excessive Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): Institutes Health Grant HL126796