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 β2-TG mice (transgenic mice with cardiac-restricted overexpression of β2-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 β2-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 β2-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 β2-TG compared with NTG mice. These differences were associated with a higher content of pre-existing fibril collagen in the normal myocardium of β2-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 metalloproteinase-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.
Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction
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Lu Fang, Xiao-Ming Gao, Chrishan S. Samuel, Yidan Su, Yean Leng Lim, Anthony M. Dart, Xiao-Jun Du; Higher levels of collagen and facilitated healing protect against ventricular rupture following myocardial infarction. Clin Sci (Lond) 1 August 2008; 115 (3): 99–106. doi: https://doi.org/10.1042/CS20070365
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