Published Online
on November 11, 2002

A more recent version of this article appeared on December 3, 2002

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Submitted on July 8, 2002
Revised on August 23, 2002
Accepted on August 24, 2002

Expression and Regulation of ST2, an Interleukin-1 Receptor Family Member, in Cardiomyocytes and Myocardial Infarction

Ellen O. Weinberg PhD, Masahisa Shimpo MD, PhD, Gilles W. De Keulenaer MD, PhD, Catherine MacGillivray , Shin-ichi Tominaga MD, PhD, Scott D. Solomon MD, Jean-Lucien Rouleau MD, and Richard T. Lee MD^*

From the Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Mass; Department of Biochemistry (S.T.), Jichi Medical School, Tochigi, Japan; and Division of Cardiology (J.-L.R.), Toronto General Hospital, Toronto, Ontario, Canada.

^* To whom correspondence should be addressed. E-mail: rlee{at}rics.bwh.harvard.edu.

Background—We identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes and hypothesized that ST2 participates in the acute myocardial response to stress and injury.

Methods and Results—ST2 mRNA was induced in cardiac myocytes by mechanical strain (4.7±0.9-fold) and interleukin-1 (2.0±0.2-fold). Promoter analysis revealed that the proximal and not the distal promoter of ST2 is responsible for transcriptional activation in cardiac myocytes by strain and interleukin-1. In mice subjected to coronary artery ligation, serum ST2 was transiently increased compared with unoperated controls (20.8±4.4 versus 0.8±0.8 ng/mL, P<0.05). Soluble ST2 levels were increased in the serum of human patients (N=69) 1 day after myocardial infarction and correlated positively with creatine kinase (r=0.41, P<0.001) and negatively with ejection fraction (P=0.02).

Conclusions—These data identify ST2 release in response to myocardial infarction and suggest a role for this innate immune receptor in myocardial injury.

Key words: stress • receptors • creatine kinase • interleukins • infarction

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