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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Luther DJ,Thodeti CK,Shamhart PE,Adapala RK,Hodnichak C,Weihrauch D,Bonaldo P,Chilian WM,Meszaros JGdoi
10.1161/CIRCRESAHA.111.252734subject
Has Abstractpub_date
2012-03-16 00:00:00pages
851-6issue
6eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.111.252734journal_volume
110pub_type
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