S100B Expression Modulates Left Ventricular Remodeling After Myocardial Infarction in Mice

Abstract

Background-S100B, a 20-kDa, Ca 2ϩ -binding dimer, is a putative intrinsic negative regulator of myocardial hypertrophy expressed after myocardial infarction. S100B-overexpressing transgenic (TG) and S100B-knockout (KO) mice have been generated to assess the consequences of S100B expression and altered hypertrophy after infarction. Methods and Results-We compared 21 wild-type (WT), 20 TG, and 24 KO mice over 35 days after experimental myocardial infarction with sham-operated controls (nϭ56). Of those, 4 WT-infarcted mice, 7 TG-infarcted mice, and 1 KO-infarcted mouse and no sham-operated mice died during the observation period. Among survivors, echocardiography, hemodynamic studies, and postmortem examination indicated that the WT and KO groups of infarcted mice mounted a hypertrophic response that was augmented in KO mice. The S100B-overexpressing TG group did not develop hypertrophy but demonstrated increased apoptosis. The postinfarct end-diastolic pressure was lower in KO mice than in WT mice, in accordance with other structural, hemodynamic, and functional parameters, which suggests that abrogation of S100B expression augmented hypertrophy, decreased apoptosis, and was beneficial to preservation of cardiac function within this time frame. Conclusions-S100B regulates the hypertrophic response and remodeling in the early postinfarct period and represents a potential novel therapeutic target. (Circulation. 2005;111:598-606.)

RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury

“…S100B expression was observed in ischemic heart disease [27] . S100B expression was also observed in myocardial infarction and S100B-deficient mice were beneficial to preservation of cardiac function herein [28] . Pelinka et al [29] showed that circulating S100B levels increased several hours after renal I/R but did not describe expression in the kidney.…”

RAGE and Modulation of Ischemic Injury in the Diabetic Myocardium

“…In the isolated perfused heart, ischemic rat hearts release S100b (43). Studies have linked S100b to maladaptive remodeling after experimental infarction in mouse models (44). Our recent studies, performed in the absence of diabetes, demonstrated that a primary stimulus to release and recruitment of the RAGE axis ensues primarily from the ischemic insult (45).…”

Stopping the Primal RAGE Reaction in Myocardial Infarction

“…However, in the S100b null mice, these pathological effects were greatly reduced. 7 Taken together, these considerations suggest that each of these RAGE ligand families may contribute to I/R injury in the heart. Experiments with the soluble ligand-binding decoy of RAGE, soluble or sRAGE, supported that binding up RAGE ligands and blocking their access to the cell surface receptor imparted cardioprotection.…”

“…Furthermore, evidence suggests that RAGE ligand S100b, a member of the S100/ calgranulin family of proinflammatory species, may mediate ventricular injury. [7][8] Transgenic mice expressing S100b (under control of its own promoter) and S100b null mice were studied by Tsoporis and colleagues. In those studies, the left anterior descending (LAD) coronary artery was ligated without reperfusion.…”

“…In those studies, the left anterior descending (LAD) coronary artery was ligated without reperfusion. 7 Pathogenic effects of S100b on apoptosis, hypertrophy, and cardiac function were demonstrated in the S100b-expressing transgenic mice. However, in the S100b null mice, these pathological effects were greatly reduced.…”