S100B expression modulates left ventricular remodeling after myocardial infarction in mice.
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.


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.
Tsoporis
James N
JN
Division of Cardiology, St Michael's Hospital, Toronto, Ontario, Canada.
Marks
Alexander
A
Haddad
Abraham
A
Dawood
Fayez
F
Liu
Peter P
PP
Parker
Thomas G
TG
D000818:Animals; D017209:Apoptosis; D015870:Gene Expression; D006321:Heart / Q000196:embryology; D006352:Heart Ventricles / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D014463:Ultrasonography; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse