Popeye domain-containing 1 is down-regulated in failing human hearts

Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress. However, it has never been explored in human hearts. In biopsies from non-failing and failing human hearts, we examined the cellular distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs. POPDC1 was visualized by immunohistochemistry and estimated by Western immunoblotting. The mRNA levels of POPDC1-3 and ß myosin heavy chain (MYHC7) were assessed using reverse transcription/quantitative polymerase chain reaction. POPDC1 was predominantly localized in the sarcolemma with an enhanced expression in the intercalated discs. In failing hearts, many cardiomyocytes appeared deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed in the four heart chambers with higher transcript levels in the ventricles compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA and protein in the left ventricle. Correlation analyses of mRNA levels among the failing heart specimens indicated the coordinated regulation of POPDC1 with POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression is modified in end-stage heart failure in humans in a manner suggesting regulatory and/or functional differences between the three family members and that POPDC1 is particularly susceptible to this condition.