Lumican-Null Mice Are Relating to the Disorganization of the Elastic Network in Cardiovascular System

The extracellular matrix (ECM) plays a critical role in the development, growth and biomechanical properties of virtually every organ system. It follows that mutations of ECM components have detrimental effects on the assembly of individual matrices and the fitness of the whole organism. We focus on lumican, one of the ECM, which may affect the function of the vascular system. Lumican is a member of a small leucine-rich proteoglycan family. Members of this family play an important role in cell migration and proliferation during embryonic development, tissue repair, and tumor growth. Lumican is reported to be overexpressed during the wound-healing process in the cornea and ischemic and reperfused heart. Recently, one study found that lumican mRNA and its protein are expressed in cultured vascular smooth muscle cells (VSMCs) from the rat aorta. In human atherosclerotic tissues, lumican protein was prominently localized in the thickened intimal stroma indicating that the lumican protein is mainly synthesized by intimal and medial VSMCs. Therefore, lumican contributes to collagen fibrillogenesis of coronary atherosclerosis. Moreover, lumican has been shown differentially expressed between dilated cardiomypathy and hypertrophic cardiomyopathy. Recently, we detected the diffuse disruption of elastic fiber architecture and thickening of the aortic media in lumican-null mice. All the previous studies imply that lumican play a novel role in the arthrosclerosis, acute coronary syndrome, cardiac hypertrophy and heart failure. We will to elucidate the detailed the roles and mechanisms of lumican in cardiovascular system by using the lumican-null mice animal models as bellow: Specific Aim 1: T To analyze in detail the time course and specific vascular disease in lumican knockout mice Specific Aim 2: To dissect the physical characteristics and molecular pathways between lumican and atherosclerosis, including vascular injury models, hyperlipidemia and neointima formation. 表 C011 共 2頁 第 1 頁 Specific Aim 3: To dissect the molecular pathways between lumican and cardiac injury models, including ischemia/reperfusion and myocardial infarction. Specific Aim 4: To dissect the molecular pathways between lumican and various cardiomyopathies, including physiologic and pathologic hypertrophy, and dilated heart failure.

Project ID:PC9709-1231
External Project ID:NSC97-2314-B182-028-MY2