Absence of Type VI Collagen Paradoxically Improves Cardiac Function, Structure, and Remodeling After Myocardial Infarction

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Abstract

Rationale:

We previously reported that type VI collagen deposition increases in the infarcted myocardium in vivo. To date, a specific role for this nonfibrillar collagen has not been explored in the setting of myocardial infarction (MI).

Objective:

To determine whether deletion of type VI collagen in an in vivo model of post-MI wound healing would alter cardiac function and remodeling in the days to weeks after injury.

Methods and Results:

Wild-type and Col6a1−/− mice were subjected to MI, followed by serial echocardiographic and histological assessments. At 8 weeks after MI, infarct size was significantly reduced, ejection fraction was significantly preserved (43.9%±3.3% versus 29.1%±4.3% for wild-type), and left ventricular chamber dilation was attenuated in the Col6a1−/− MI group (25.8%±7.9% increase versus 62.6%±16.5% for wild-type). The improvement in cardiac remodeling was evident as early as 10 days after MI in the Col6a1−/− mice. Myocyte apoptosis within the infarcted zones was initially greater in the Col6a1−/− group 3 days after MI, but by day 14 this was significantly reduced. Collagen deposition also was reduced in the infarcted and remote areas of the Col6a1−/− hearts. The reductions in chronic myocyte apoptosis and fibrosis are critical events leading to improved long-term remodeling and functional outcomes.

Conclusions:

These unexpected results demonstrate for the first time that deletion of type VI collagen in this knockout model plays a critical protective role after MI by limiting infarct size, chronic apoptosis, aberrant remodeling, and fibrosis, leading to preservation of cardiac function.

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