Study on the pathogenesis of peripertum cardiomyopathy using genetically modified mouse model

本研究通过G蛋白偶联受体超家族成员APJ的心肌细胞特异性高表达，建立了围产期心肌病(MHC-APJ)的动物模型。哺乳期的MHC-APJ母亲表现出心功能降低、心脏增大、心脏纤维化，以及心力衰竭标志性基因的mRNA表达增强。我们发现“哺乳”在MHC-APJ的上述表型的发病机制中是必不可少的，因为这些表型在非妊娠或非哺乳期的MHC-APJ母亲中没有观察到。通过详尽的基因表达分析，我们确定了几个只在哺乳期MHC-APJ小鼠心脏中发生变化的基因。我们认为这些基因可能是APJ信号增强和哺乳共同作用所致的围产期心肌病的候选基因。

In this study, we established an animal model for "peripertum cardiomyopathy" (MHC-APJ) by cardiomyocyte-specific overexpression of APJ, a member of G-protein coupled receptor superfamily and expressing mainly in cardiovascular system. The lactating MHC-APJ mother exhibited reduced cardiac function, enlargement of the heart, cardiac fibrosis, and enhanced mRNA expression of the marker genes of heart failure. We found that "lactation" is essential for the pathogenesis of above phenotypes in MHC-APJ because those were not observed in non-pregnant or non-lactating MHC-APJ mother. By using an exhaustive gene expression analysis, we identified the several genes that changed only in the heart from lactating MHC-APJ mice. We consider these genes to be the candidates of the pathogenesis of peripertum cardiomyopathy induced by the combined action of enhanced APJ signaling and lactation in mice.