Molecular mechanism of the process from atherosclerotic lesion formation to plaque rupture

点击翻译按钮获取中文摘要

In this study we tried to elucidate the molecular mechanism involved in the process from atherosclerotic lesion formation to plaque rupture, a phenomenon involved in acute coronary syndrome. Kume in our group has found that the formation of a soluble form of LOX-1 (oxidized LDL receptor) was increased in the blood by thrombus formation in a transgenic mouse overexpressing human LOX-1 specifically in endothelia cells and smooth muscle cells. He also found that this soluble form of LOX-1 was increased in patients of acute coronary syndrome, indicating that this molecule could be a marker for acute coronary syndrome as well as for the development of atherosclerotic lesions. Arai, Kume, and Yokode in our group found that the novel oxidized LDL receptor, SR-PSOX (scavenger receptor for phosphatidylserine and oxidized low-density lipoprotein), which we cloned is the same molecule as α-chemokine, CXCL16. Our data showed that CXCL16 could induce angiogenesis by increasing endothelial proliferation, chemotaxis, and tube formation. The MAP kinase (ERK) was found to be involved in CXCL16-induced angiogenesis. Horiuchi in our group established a semi-intact assay to analyze the molecular mechanism of aggregation and granule secretion of platelets using permeabilized platelets. Using this system he found that Rab27 regulated the dense core granule secretion in platelets by employing its binding protein, Munc13-4. Nakamura in our group found that fibulin-5 mRNA was increased in the mouse atherosclerotic lesions and pulmonary hypertension model.