Chromatin Remodeling and Cell Cycle Activity in Periinfarction Myocardium.
Bo Ye, Weiko Mao, Loralee McMahon, Qi Yang, Haodong Xu, Faqian Li. University of Rochester Medical Center, NY
Background: Proliferative activity of cardiac myocytes has been observed in periinfarction myocardium. To access DNA template, chromatin remodeling and DNA unwinding is required. Enhancer of zeste homolog 2 (EZH2), a key component of polycomb repressive complex 2, regulates cell proliferation by histone H3 methylation at lysine 27. Brahma-related gene 1 (Brg1) is the ATPase subunit of a large chromatin remodeling complex. The aim of this study was to determine if EZH2 and Brg1 expressed in periinfarction myocardium.
Design: Ten cases of left ventriculectomy for the placement of left ventricle (LV) assistance device in patients with acute myocardial infarction less than 2 week old and 2 cases of normal hearts unsuitable for implantation were studied. Four micron sections of LV were stained with antibodies against EZH2 (Leica, clone 6A10, 1:100), Brg-1 (Santa Cruz, clone G-7, 1:100), and Ki-67 (DAKO, clone MIB1, 1:100) using a kit (EnVisonTM Flex+ Dako) and an automated immunostainer.
Results: Rare non-cardiac myocytes in normal hearts and remote areas of infarcted hearts showed nuclear positivity for EZH2 and Ki-67, but no staining for these markers was detected in cardiac myocytes in the same areas. In periinfarction myocardium, there was significant increase in Ki-67 and Brg1 positive non-cardiac myocytes. Strong nuclear staining for these markers was also detected in 5 to 10% cardiac myocytes in periinfarction zones. More importantly, serial section staining revealed that there was co-expression of these markers in cardiac myocytes of periinfarcion myocardium. Brg-1 was weakly expressed in both cardiac myocyte and non-cardiac myocytes in normal hearts and remote areas of infarcted hearts. There was significant increase in Brg-1 expression in periinfarcion myocardium.
Conclusions: Cell cycle entry in cardiac myocytes of periinfarction myocardium is accompanied by increased expression of EZH2 and Brg1. This result suggests there is chromatin remodeling and histone modification in cardiac myocytes of periinfarction myocardium.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 33, Wednesday Afternoon