Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction
Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction
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DOI：
10.1042/cs20070365
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发表时间：
2008-08-01
期刊：
影响因子：
6
通讯作者：
Du, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Fang, Lu;Gao, Xiao-Ming;Du, Xiao-Jun
心肌梗死后心脏破裂的机制尚不完全清楚。大多数实验室物种（包括大鼠）中未报告破裂，但小鼠中确实发生破裂。我们之前曾报道过，与NTG（非转基因）同窝小鼠相比，β（2）-TG小鼠（β 2肾上腺素能受体心脏限制性过表达的转基因小鼠）的破裂发生率较低。我们假设啮齿类动物和特定小鼠品系之间破裂发生率的差异是由于MI后胶原蛋白含量的差异。在本研究中，我们比较了β（2）-TG和NTG小鼠之间以及小鼠和大鼠之间心肌梗死后基质重塑的差异。通过结扎左冠状动脉主干诱导MI。MI后，抗张强度，不溶性和可溶性胶原含量和明胶酶的表达在梗死和非梗死心肌。与NTG小鼠相比，β（2）-TG更好地保留了TTR测量的拉伸强度[断裂张力;分别为假手术组值的88 +/- 14和58 +/- 3（P < 0.05）;与129 sv小鼠相比，大鼠分别为假手术组值的108 +/- 7和32 +/- 4%（P < 0.01）]，心肌梗死后急性心肌梗死范围扩大程度大鼠较小鼠轻，β 2-TG较NTG小鼠轻。这些差异与β（2）-TG小鼠正常心肌中预先存在的纤维胶原含量高于NTG小鼠（1.6倍）或大鼠高于129 sv小鼠（2倍）以及梗死心肌中纤维化愈合加速有关。此外，与129 sv小鼠相比，在大鼠的梗死心肌中观察到MMP-9（基质金属蛋白酶-9）活性的增加不太明显。我们得出结论，较高的胶原蛋白水平与促进梗死的纤维化愈合有关，并保持梗死心肌的拉伸强度，从而防止心脏破裂和急性心室重塑。
The mechanism of cardiac rupture after MI (myocardial infarction) is not fully understood. Rupture has not been reported in most laboratory species, including the rat, but does occur in mice. We have reported previously that beta(2)-TG mice (transgenic mice with cardiac-restricted overexpression of beta 2-adrenergic receptors) had a lower incidence of rupture compared with NTG (non-transgenic) littermates. We hypothesized that the difference in the incidence of rupture between rodents and specific mouse strains is due to the difference in collagen content following MI. In the present study, we compared the difference in matrix remodelling post-MI between beta(2)-TG and NTG mice and between mice and rats. MI was induced by ligation of the left main coronary artery. Following MI, tensile strength, insoluble and soluble collagen content and gelatinase expression were determined in the infarcted and non-infarcted myocardium. Better preserved tensile strength measured as TTR [tension-to-rupture; 88 +/- 14 and 58 +/- 3 % of the respective sham group values for beta(2)-TG compared with NTG mice (P < 0.05); 108 +/- 7 and 32 +/- 4% of the respective sham group values for rats compared with 129sv mice (P < 0.01)] and less severe acute infarct expansion after MI were found in rats compared with mice or in beta(2)-TG compared with NTG mice. These differences were associated with a higher content of pre-existing fibril collagen in the normal myocardium of beta(2)-TG compared with NTG mice (1.6-fold) or rats compared with 129sv mice (2-fold) and an accelerated fibrotic healing in the infarcted myocardium. Additionally, a less pronounced increase in MMP-9 (matrix metal loproteinase-9) activity was observed in the infarcted myocardium of rats compared with 129sv mice. We conclude that a higher collagen level is associated with facilitated fibrotic healing of an infarct and preserves the tensile strength of infarcted myocardium, thereby preventing cardiac rupture and acute ventricular remodelling.