Tsoporis James N, Marks Alexander, Haddad Abraham, Dawood Fayez, Liu Peter P, Parker Thomas G
Division of Cardiology, St Michael's Hospital, Toronto, Ontario, Canada.
Circulation. 2005 Feb 8;111(5):598-606. doi: 10.1161/01.CIR.0000154554.65287.F5.
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.
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.
S100B regulates the hypertrophic response and remodeling in the early postinfarct period and represents a potential novel therapeutic target.
S100B是一种20 kDa的钙离子结合二聚体，是心肌梗死后表达的一种假定的心肌肥大内在负调节因子。已培育出S100B过表达转基因（TG）小鼠和S100B基因敲除（KO）小鼠，以评估S100B表达及梗死后肥大改变的后果。
我们将21只野生型（WT）小鼠、20只TG小鼠和24只KO小鼠在实验性心肌梗死后35天与假手术对照组（n = 56）进行比较。其中，4只WT梗死小鼠、7只TG梗死小鼠和1只KO梗死小鼠在观察期死亡，假手术小鼠无死亡。在存活小鼠中，超声心动图、血流动力学研究及尸检表明，WT和KO梗死小鼠组出现了肥大反应，且KO小鼠的肥大反应增强。S100B过表达的TG组未发生肥大，但凋亡增加。KO小鼠梗死后舒张末期压力低于WT小鼠，这与其他结构、血流动力学和功能参数一致，提示在该时间段内S100B表达缺失可增强肥大、减少凋亡，并有利于心脏功能的保存。
S100B在梗死后早期调节肥大反应和重塑，是一个潜在的新型治疗靶点。
