Info

Day 14

Day 90

Fig. 2. ST2 protein levels in circulation of human patients after MI. Serial blood samples from 69 patients from the HEART study were analyzed for ST2 by enzyme-linked immunosorbent assay. ST2 was significantly increased on d 1 after MI compared with d 14 and d 90. ANOVA, analysis of variance. (Reproduced from ref. 15.)

Day 1

Day 14

Day 90

Fig. 2. ST2 protein levels in circulation of human patients after MI. Serial blood samples from 69 patients from the HEART study were analyzed for ST2 by enzyme-linked immunosorbent assay. ST2 was significantly increased on d 1 after MI compared with d 14 and d 90. ANOVA, analysis of variance. (Reproduced from ref. 15.)

colleagues showed that membrane-anchored ST2 (ST2L) mRNA was expressed in mouse T helper type 2 (Th2) cells but not Th1 cells (9,10). This finding was confirmed by others (10-13). Hence, ST2L appears to be a marker of Th2 cells.

In studies searching for new genes induced by mechanical stress, we used DNA microarray technology to identify ST2 as a gene markedly induced by cyclic mechanical strain in cultured cardiac myocytes. This system models on a cellular level the increase in ventricular stress imposed on the myocardium during hemodynamic overload (14). Northern analysis confirmed the DNA microarray result demonstrating rapid induction of ST2 mRNA (within 1 h) in cultured cardiac myocytes subjected to mechanical strain sustained for 15 h (15). In addition to mechanical strain, IL-1P and phorbol ester, but not LPS (a ligand for the toll receptor) or TNF-a, induced ST2 mRNA, suggesting selectivity for the induction of ST2 in cardiac myocytes.

Based on our in vitro findings in cultured cardiac myocytes, and because ST2 is a secreted protein that is detected in human serum (16), we hypothesized that serum levels of ST2 may be elevated in patients following MI, a condition in which the remaining viable myocardium bears additional hemodynamic stress. Serum ST2 levels were measured on d 1, 14, and 90 after MI in patients enrolled in the Healing and Early Afterload Reducing Trial (HEART) (15). HEART evaluated the safety and effectiveness ofthe angio-tensin-converting enzyme inhibitor ramipril beginning on d 1 vs d 14 after MI (17-19). Circulating serum ST2 levels were elevated on d 1 after MI compared with d 14 and 90 (p < 0.001) (Fig. 2). Serum ST2 levels on d 1 correlated inversely with echocardiographic ejection fraction, suggesting an association between hemodynamic stress and ST2 levels. In addition, ST2 levels correlated positively with creatine kinase, a marker ofcellular injury postinfarction.

Was this article helpful?

0 0

Post a comment