Department of Internal Medicine, Section on Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cardiol Rev. 2009 Nov-Dec;17(6):293-9. doi: 10.1097/CRD.0b013e3181bf4ab4.
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.
心肌梗死后的心脏破裂是一种罕见的灾难性事件。尽管已经描述了破裂的临床特征，但在心肌梗死后患者中，这种结果的遗传和分子影响还不太确定。在小鼠中，已经开发了至少 17 种遗传模型，这些模型增强或抑制了心肌梗死后破裂的可能性。本综述的目的是描述这些最新进展，同时认识到几乎所有信息都是从心肌梗死后游离壁破裂的小鼠模型中获得的。尽管同样的遗传决定因素可能适用于间隔和乳头肌破裂，但在心脏内不同解剖部位，破裂风险的独特调节剂仍然存在。候选基因也可能影响人类的破裂，尽管这一结论必须得到证实。这些小鼠模型将有助于指导未来针对患者的蛋白质组学和基因组学研究，并且可能已经提示了某些基本途径。例如，心肌梗死后胶原产生和稳定的关键作用可能指导治疗策略，以增强胶原交联并限制其降解，从而降低破裂率并增强心肌愈合。
