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

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&bgr; (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&bgr;. 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.

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