MMP13 prevents cardiac injury and left ventricular dysfunction in Coxsackievirus B3-induced acute myocarditis

Abstract

Background: Myocarditis is an important cause for cardiac failure, especially in younger patients, followed by the development of cardiac dysfunction and death. The present study investigated whether the deficiency of matrix metalloproteinase-13 influences cardiac inflammation and function in murine coxsackievirus B3 (CVB3)-induced myocarditis. Methods and material: Matrix metalloproteinase-13 knockout mice (MMP-13-/-) and their wild-type controls (WT) were infected with CVB3 to induce acute myocarditis. Seven days after viral infection, left ventricular (LV) function was estimated by conductance catheter technique, cardiac remodeling and inflammatory and antiviral response by immunohistochemistry, PCR and western blot analyses. Seven days after CVB3 infection, an increased invasion of CD11b and CD68 positive cells into the myocardium was documented. This was followed by an overwhelming proinflammatory cytokine induction and an increase in viral load 7 days after infection, which was significantly higher in the MMP-13-/- mice compared to the WT animals (p<0.05). Moreover, cardiac apoptosis, fibrosis and remodeling were deteriorated in MMP-13-/- animals after viral infection (p<0.05). This was associated with a significant impairment in systolic and diastolic LV function in the MMP-13-/- mice compared to the WT animals (p<0.05). Conclusion: Loss of MMP-13 leads to an overwhelming cardiac immune response and to an deterioration in cardiac function. MMP13 is required for preservation of the hemodynamic function and the maintenance of matrix assembly during acute myocarditis.