Human eHAND, but not dHAND, is down-regulated in cardiomyopathies

Aruna Natarajan, Hiroyuki Yamagishi, Ferhaan Ahmad, Duanxiang Li, Robert Roberts, Rumiko Matsuoka, Sandra Hill, Deepak Srivastava

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30 Citations (Scopus)

Abstract

The progression of cardiomyopathy to congestive heart failure is often associated with the expression of fetal cardiac-specific genes. In mice, the basic helix-loop-helix transcription factors, dHAND and eHAND, are expressed in a cardiac chamber-specific fashion and are essential for fetal cardiac development, but are down-regulated in the adult. Their expression in specific chambers of healthy and diseased human hearts has not been studied previously. Human dHAND and eHAND were mapped to human chromosomes 4q33 and 5q33, respectively, by fluorescent in situ hybridization, RNA from the four chambers of healthy human adult hearts, and from hearts of patients with several forms of cardiomyopathy, was obtained and assayed for dHAND and eHAND expression. Unlike in mice. dHAND expression was observed in all four chambers of the healthy human adult heart, but was diminished in the right atrium. In contrast, eHAND was expressed in the right and left ventricles, but was downregulated in both atrial chambers. We examined tissue from 15 human cardiomyopathic hearts obtained during cardiac transplantation or by endomyocardial biopsy for alterations in HAND gene expression. dHAND expression was unchanged in all forms of cardiomyopathy tested. However, cardiac expression of eHAND was severely down-regulated in six of six patients with ischemic cardiomyopathy and six of six patients with dilated cardiomyopathy. This study demonstrates that human dHAND and eHAND have unique spatial patterns of expression within human cardiac chambers. Downregulation of eHAND in ischemic and dilated cardiomyopathy suggests a correlation between eHAND dysregulation and the evolution of a subset of cardiomyopathies.

Original languageEnglish
Pages (from-to)1607-1614
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number9
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Keywords

  • Cardiomyopathy
  • Human
  • dHAND
  • eHAND

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Natarajan, A., Yamagishi, H., Ahmad, F., Li, D., Roberts, R., Matsuoka, R., Hill, S., & Srivastava, D. (2001). Human eHAND, but not dHAND, is down-regulated in cardiomyopathies. Journal of Molecular and Cellular Cardiology, 33(9), 1607-1614. https://doi.org/10.1006/jmcc.2001.1434