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(Circulation. 2005;111:598-606.)
© 2005 American Heart Association, Inc.

Heart Failure

S100B Expression Modulates Left Ventricular Remodeling After Myocardial Infarction in Mice

James N. Tsoporis, PhD; Alexander Marks, MD; Abraham Haddad, MSc; Fayez Dawood, DVM; Peter P. Liu, MD; Thomas G. Parker, MD

From the Division of Cardiology, St Michael’s Hospital (J.N.T., A.H., T.G.P.), and Banting and Best Department of Medical Research (A.M.), Heart and Stroke/Richard Lewar Centre of Excellence (F.D., P.P.L.), University of Toronto, Toronto, Canada.

Reprint requests to Thomas G. Parker, Division of Cardiology, St Michael’s Hospital, 30 Bond St, Queen Wing, Room 6-044, Toronto, Ontario M5B 1W8, Canada. E-mail parkertg{at}smh.toronto.on.ca

Received June 14, 2004; revision received September 30, 2004; accepted October 22, 2004.

Background— S100B, a 20-kDa, Ca²⁺-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 (n=56). 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.

Key Words: hypertrophy • proteins • myocardial infarction • apoptosis • remodeling

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