Genetic mouse models of post-MI cardiac rupture suggest that pathways involving collagen production and stabilization are critical and may direct future therapies to enhance myocardial healing.
May guide therapy development targeting collagen stabilization post-MI; leaves open translation from mouse models to clinical use.
Cardiac rupture after a myocardial infarction is an uncommon event with devastating consequences. Although the clinical features of rupture have been described, the genetic and molecular influences on this outcome in patients are less certain. In mice, at least 17 genetic models have been developed that enhance or suppress the likelihood of rupture postmyocardial infarction. The purpose of this review is to describe these recent advances, recognizing that nearly all of the information has been obtained from mouse models of free wall rupture. Although it is probable that the same genetic determinants apply to septal and papillary muscle rupture, the possibility remains that there are unique modulators of risk for rupture at differing anatomic sites within the heart. It is likely that the candidate genes also influence rupture in humans, although this conclusion must be confirmed. The mouse models will be helpful to direct future proteomic and genomic studies in patients and may already suggest certain fundamental pathways. For example, the essential role of collagen production and stabilization postmyocardial infarction may direct therapies to enhance collagen cross-linking and limit its degradation as a strategy to reduce rates of rupture and enhance myocardial healing.
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Sane et al. (2009) studied this question.
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