Targeted deletion of the MMP-9 gene significantly restored endocardial endothelial-myocyte coupling and attenuated myocardial contractile dysfunction in mice with chronic volume overload.
Does targeted deletion of MMP-9 prevent endocardial endothelial-myocyte uncoupling and myocardial contractile dysfunction in a mouse model of chronic volume overload?
Targeted deletion of MMP-9 restores endocardial endothelial-myocyte coupling in a mouse model of chronic volume overload, suggesting MMP-9 activation causes EM uncoupling and myocardial contractile dysfunction.
p-value: p=<0.05
Chronic volume overload (VO) on the left ventricle (LV) augments redox stress and activates matrix metalloproteinase (MMP) which causes the endocardial endothelial-myocyte (EM) disconnection leading to myocardial contractile dysfunction. VO-induced MMP-9 activation impairs cardiac functions, in part by endothelial endocardial apoptosis, but the role of MMP-9 on EM functions remains obscure. We conjecture that chronic VO activates MMP-9 and causes EM uncoupling. Arteriovenous fistula (AVF) was created in genetically identical wild type (WT) mice (FVB/NJ) and MMP-9 knockout mice (MMP-9KO, FVB.Cg-MMP9(tm1Tvu)/J). Sham-operated mice were used as controls. Before experimentation the phenotype analysis of MMP-9KO mice was carried out. In-gel-gelatin zymography for MMP-9 activation was performed on LV homogenates. The EM functions were determined on LV rings using tissue myobath. We report a decrease in MMP-9 activity in left ventricular myocardial extracts in MMP-9 deficient mice after AVF. The responses to drugs affecting cardiac functions (acetylcholine (Ach), nitroprusside and bradykinin) were attenuated in AVF mice suggesting the impairment of EM coupling. Interestingly, the EM functions were restored in the MMP-9 deficient mice after AVF. We suggest a direct cause-and-effect relationship between MMP-9 activation and EM uncoupling in LV myocardium after chronic VO and the possible involvement of MMP-9 in myocardial contractile performance.
Moshal et al. (Tue,) conducted a other in Chronic volume overload-induced heart failure (n=24). Targeted deletion of MMP-9 (MMP-9 knockout) vs. Wild type (WT) mice was evaluated on Endocardial endothelial-myocyte coupling (relaxation to acetylcholine and nitroprusside) (p=<0.05). Targeted deletion of the MMP-9 gene significantly restored endocardial endothelial-myocyte coupling and attenuated myocardial contractile dysfunction in mice with chronic volume overload.