心肌梗死在临床上是多发疾病，研究其发病机理对其预防和治疗有重要意义。Hand1是碱性螺旋-环-螺旋转录因子家族的一员，近来研究发现,Hand1基因在缺血性心肌病人（心肌梗塞病）心脏中表达降低。我们最近研究显示，野生型小鼠给予左室冠状动脉结扎后一周内Hand1在RNA水平明显降低。这些结果提示Hand1基因可能参与了心肌梗塞的发展过程。但是Hand1下调对心肌梗死发展过程的病理生理学意义仍不清楚。为弄清这一问题，我们对Hand1基因杂合敲除小鼠与同窝对照小鼠行左室冠状动脉结扎制成心肌梗死模型，发现Hand1单倍缺失的小鼠在MI手术后存活时间更长，表明Hand1缺失对心梗有保护作用。接下来本项目拟制作更多的心梗模型并运用病理组织学、生物化学和分子生物学技术来系统分析Hand1的量在心肌梗死过程中的作用，揭示新的心肌梗死的病理机制,为临床预防和治疗心肌梗死提供理论指导。

Myocardial infarction (MI) has a high incidence in clinical patients.Disection of its pathogenesis has a high impact on its prevention and treatment.Hand1 is a member of the basic helix-loop-helix transcription factor family.It has been founded that Hand1 expression is downregulated in ischemic cardiomyopathy compared with normal heart tissue.The preliminary data support this proposal is that we recently found that mRNA expression of Hand1 was also downregulated in mice one week after ligation of left ventricular coronary artery. These results suggest that Hand1 may be involved in myocardial infarction. However the functional role of Hand1 in the development of myocardial infarction is still unknown. In order to clarify this question, we did left ventricular cornary artery ligation on Hand1 heterozygous knock out mice and wild-type littermates to make myocardial infarction model, and found that Hand1 heterozygous knockout mice survived longer than the control mice.This result suggests that haploinsufficiency of Hand1 can protect mice under myocardial infarction.In this proposed project, we will make more myocardial infarction mouse model and elucidate the role of Hand1 and its involved pathological molecular mechanisms in myocardial infarction uing histopathologic, biochemical and molecular biological techniques.The outcome of this project will open a novel avenue to guide the clinical prevention and treatment of MI.