Abstract 20099: Adiponectin Inhibits Maladaptive Cardiac Remodeling in Cardiac Disease by Increasing Matrix Metalloproteinase-9 Activity

Introduction: Adiponectin (APN) is an immunomodulatory adipocytokine that inhibits left ventricular hypertrophy induced by pressure overload as well as hypertension. Here, we investigated whether APN inhibits adverse extracellular matrix (ECM) remodeling in in experimental models of myocardial infarction (MI) and coxsackievirus B3 (CVB3) myocarditis by affecting matrix metalloproteinase (MMP) expression and its possible mechanisms. Methods: Experimental CVB3 myocarditis and experimental MI were induced in APN-KO and wild-type (WT) C57/BL6J mice. RNA and protein expression/enzymatic activity of MMPs was quantified by qRT-PCR and zymography, respectively. Activation status of protein kinases was determined by immunoblot. Results: In cultured cardiac myocytes and fibroblasts APN induced MMP-9 gene and protein expression by activation of AMPK and MEK1 without affecting MMP-2, MMP-3 and MMP-13. Inhibition with PD098059 and Compound C almost completely abolished MMP-9 up-regulation in this setting. AMPK as well...