Submitted on November 9, 2006
Accepted on February 20, 2007
Gene profiling during regression of pressure overload-induced cardiac hypertrophy
Dong Kwon Yang1, Bo Youn Choi1, Young-Hoon Lee2, Young-Gyu Kim3, Myeong-Chan Cho3, Seong-Eui Hong1, Do Han Kim1, Roger J Hajjar4, and Woo Jin Park1*
1 Life Science, Gwangju Institute of Science and Technology, Gwangju, Korea, Republic of
2 Oral Anatomy, Chonbuk National University, Jeonju, Korea, Republic of
3 Internal Medicine, Chungbuk National University, Cheongju, Korea, Republic of
4 Cardiovascular Research Center, MGH, Charlestown, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: wjpark{at}gist.ac.kr.
Regression of cardiac hypertrophy and improvement of the functional capacity of failing hearts has reportedly been achieved by mechanical unloading in cardiac work. In this study, cardiac hypertrophy was first induced in rats by transverse aortic constriction (TAC), and then mechanically unloaded by relieving the constriction after significant cardiac hypertrophy had developed. Hypertrophy was significantly regressed at the cellular and molecular levels at day 1, 3, and 7 after constriction relief. Gene profiling analysis revealed that 52 genes out of 9,911 genes probed on a gene array were specifically upregulated during the early regression period. Among these regression-induced genes, Eyes absent 2 (Eya2) was of particular interest because it is a transcriptional cofactor involved in mammalian organogenesis as well as Drosophila eye development. Adenovirus-mediated overexpression of Eya2 in rat neonatal cardiomyocytes completely abrogated phenylephrine-induced development of cardiomyocyte hypertrophy as determined by cell size, sarcomere rearrangement and fetal gene re-expression. Our data strongly suggest that transcriptional programs distinct from those mediating cardiac hypertrophy may be operating during the regression of hypertrophy, and Eya2 may be a key regulator of one of these programs.
