Absence of type VI collagen paradoxically improves cardiac function, structure, and remodeling after myocardial infarction.
Absence of type VI collagen paradoxically improves cardiac function, structure, and remodeling after myocardial infarction.
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DOI：
10.1161/circresaha.111.252734
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发表时间：
2012-03-16
影响因子：
20.1
通讯作者：
Meszaros JG
中科院分区：
文献类型：
--
作者：
Luther DJ;Thodeti CK;Shamhart PE;Adapala RK;Hodnichak C;Weihrauch D;Bonaldo P;Chilian WM;Meszaros JG
我们以前报道，VI型胶原沉积增加在体内梗死心肌。迄今为止，这种非纤维胶原蛋白在心肌梗死（MI）中的具体作用尚未研究。确定MI后伤口愈合的体内模型中VI型胶原缺失是否会改变损伤后数天至数周内的心脏功能和重塑。对野生型（WT）和Col 6a 1-/-小鼠进行MI，随后进行系列超声心动图和组织学评估。在MI后8周，在Col 6a 1-/- MI组中，梗死面积显著减小，射血分数显著保持（43.9 ± 3.3%对WT的29.1 ± 4.3%）并且左心室（LV）腔室扩张减弱（25.8 ± 7.9%增加对WT的62.6 ± 16.5%）。早在Col 6a 1-/-小鼠MI后10天，心脏重塑的改善就很明显。MI后3天，Col 6a 1-/-组中梗死区内的心肌细胞凋亡最初较大，但到第14天，这显著减少。胶原蛋白沉积也减少了梗死和偏远地区的Col 6a 1-/-心脏。慢性肌细胞凋亡和纤维化的减少是导致改善长期重塑和功能结局的关键事件。这些意想不到的结果首次证明，在该敲除模型中VI型胶原的缺失通过限制梗死面积、慢性细胞凋亡、异常重塑和纤维化而在MI后起到关键的保护作用，从而导致心脏功能的保留。
We previously reported that type VI collagen deposition increases in the infarcted myocardium in vivo. To date, a specific role for this non-fibrillar collagen has not been explored in the setting of myocardial infarction (MI). 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. Wild type (WT) and Col6a1-/- mice were subjected to MI followed by serial echocardiographic and histological assessments. At 8 weeks post-MI, infarct size was significantly reduced, ejection fraction was significantly preserved (43.9 ± 3.3% vs. 29.1 ± 4.3% for WT) and left ventricular (LV) chamber dilation was attenuated in the Col6a1-/- MI group (25.8 ± 7.9% increase vs. 62.6 ± 16.5% for WT). The improvement in cardiac remodeling was evident as early as 10 days post-MI in the Col6a1-/- mice. Myocyte apoptosis within the infarcted zones was initially greater in the Col6a1-/- group 3 days post-MI but by day 14 this was significantly reduced. Collagen deposition was also 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. These unexpected results demonstrate for the first time that deletion of type VI collagen in this knockout model plays a critical protective role following MI by limiting infarct size, chronic apoptosis, aberrant remodeling and fibrosis leading to preservation of cardiac function.