MOLECULAR BIOLOGY AND MECHANICS OF CARDIAC INTERSTITIUM

描述(改编自申请人的摘要)：总体目标 这一提议的目的是检验这样一种假设，即SCAR各向异性是理想的 对…的正常功能有重要贡献的结构特征 邻近心肌。应聘者将考察以下角色 机械拉伸、预先存在的细胞外基质与血管内皮生长因子上调 转化生长因子-β1在定义各向异性中的作用 心肌疤痕的结构。初步研究旨在确定 近邻心肌有限变形的正常空间梯度 心肌梗死猪模型的愈合疤痕。直接测试 关于疤痕的独特结构影响功能的假说 邻近心肌申请人建议通过以下方式修改疤痕结构 在愈合过程中控制局部转化生长因子-β1的水平。其他研究，以 在猪脑梗塞模型和体外培养的心脏中进行 成纤维细胞将测试机械变形， 先前存在的基质和转化生长因子-β1对瘢痕结构和功能没有明确的定义。 临床上已知急性脑缺血的及时再通 心肌可以缩小梗塞面积，保护左心功能。 这种方法已成为冠状动脉病变后数小时内的首选治疗方法。 遮挡。有证据表明，胶原蛋白的强度和含量 再灌流的瘢痕不同于永久性闭塞的心肌。 然而，除了这些观察之外，人们对疤痕结构和 交界性心肌在冠脉闭塞及冠脉病变中的作用 再灌流。因此，作为提案的第三个目标，申请人将 观察猪心肌梗死再灌流后的结构特点和 瘢痕组织的力学性质及其交界处的功能 心肌。

DESCRIPTION (adapted from the applicant's abstract): The overall objective of this proposal is to test the hypothesis that scar anisotropy is a desired structural feature that contributes importantly to the normal function of adjacent myocardium. The applicant will examine for the roles that mechanical stretch, preexisting extracellular matrix and the upregulation of Transforming Growth Factor-b1 (TGF-b1) play in defining the anisotropic structure of the myocardial scar. Initial studies are designed to define the normal spatial gradient of finite deformation in myocardium adjacent to the healing scar in a pig model of myocardial infarction. To directly test the hypothesis that the unique structure of the scar influences function in adjacent myocardium the applicant proposes to modify scar structure by manipulating local levels of TGF-b1 during healing. Additional studies to be performed in the pig model of infarction and in vitro in cultured cardiac fibroblasts will test for the roles that mechanical deformations, preexisting matrix and TGF-b1 have on defining scar structure and function. Clinically, it is known that the timely reperfusion of acutely ischemic myocardium can reduce infarct size and preserve left ventricular function. This approach has become the treatment of choice within hours of coronary occlusion. There is evidence that strength and collagen content of reperfused scars differs from that of permanently occluded myocardium. However, beyond these observations little is known about scar structure and function of bordering myocardium in the setting of coronary occlusion and reperfusion. Thus, as a third aim of the proposal the applicant will examine in infarcted-reperfused pig myocardium the structural features and mechanical properties of scar tissue as well as function in bordering myocardium.