Transcription factor AP-2a triggers apoptosis in cardiac myocytes.

Idiopathic-dilated cardiomyopathy (IDC) is a common primary myocardial disease of unknown etiology associated with apoptosis, cardiac dilatation, progressive heart failure and increased mortality. An elevation of the transcription factor activator protein 2a (AP-2a) is involved in vertebrate embryonic development and oncogenesis. Here, we show that AP-2a protein is expressed in the human heart and increased in human failing myocardium with IDC. Adenovirus-mediated overexpression of human AP-2a triggered apoptosis and increased mRNA levels of Bcl-2 family members Bax and Bcl-x in rat cardiomyocytes. Immunohistological analysis of human myocardium revealed an increased percentage of AP-2a-positive nuclei in IDC and, interestingly, a colocalization of AP-2a-positive but not -negative cells with a caspase-cleaved fragment of poly(ADP-ribose)polymerase. We suggest AP-2a as a novel cardiac regulator implicated in the activation of apoptosis in IDC.Cell Death and Differentiation (2004) 11, 485-493. doi:10.1038/sj.cdd.4401383 Published online 30 January 2004 [ABSTRACT FROM AUTHOR]