冠動脈疾患の病態解明と新しい診断治療技術の開発

Recent evidence suggests that acute coronary syndrome（ACS）results from plaque rupture in most of the cases. Vulnerable plaques are characterized by thinning of fibrous cap, increased lipid content, decreased smooth muscle cell content, and enhanced infiltration of inflammatory cells. However, the molecular mechanism of plaque destabilization is not fully understood. Thus, there is no established method to predict and prevent ACS. We have been studying the pathogenesis of plaque progression and destabilization, using animal models and clinical specimen. ApoE-deficient mice showed exaggerated atherosclerotic lesions with aging. Accumulation of macrophages in adventitia was first detected prior to plaque formation. Proliferation of vasa vasorum was observed only after atherosclerotic lesion formation. Local delivery of an angiogenic growth factor promoted lesion formation with enhanced neovascularization in the adventitia. Periadventitial fat is distributed ubiquitously around arteries. By using fat transplantation method, we found that periadventitial fat may protect against neointimal formation after angioplasty under physiological conditions and that inflammatory changes in the periadventitial fat may play a crucial role in the pathogenesis of vascular disease accelerated by obesity. Elucidation of the pathogenesis of coronary artery diseases leads to development of new strategies to diagnose and treat acute coronary syndrome.