Haptoglobin在動脈硬化中所扮演之功能角色

Abstract

冠狀動脈及其他心血管疾病(包括心肌梗塞)是造成西方工業化國家人口死亡的主要原因。在台灣心血管疾病雖名列死亡疾病前三、四名，但在民國八十九年內因血管疾病造成死亡的人數竟高達三萬五千人次；即使利用降低膽固醇藥物(hypocholesterolemic drugs)來進行治療。以此種危險性觀之，心血管疾病仍是引起死亡的主要殺手。冠狀動脈粥狀化之病理研究中，最為人注意及採信的病理觀點為低密度脂蛋白修飾假說(LDL-modification hypothesis)，其主要觀點為冠狀動脈斑(atherosclerotic plaques)的形成是由於巨噬細胞(macrophages) 在動脈管壁內吞噬氧化修飾之低密度脂蛋白(oxidatively modified LDL)，導致平滑肌細胞的遷移及增生作用(smooth muscle cell migration and proliferation)。其中，值得注意的是了解氧化作用所受的緊迫、平滑肌細胞在intima的轉移及增生作用之各項生化角色相對地變得十分重要。

Coronary artery and other vascular diseases (including myocardial infarction, MI) are the leading cause of death in the Western industrialized countries. The mortality of the diseases are the top third-fourth in Taiwan, the number of death reached more than 35,000 in year 2001 and has since become the leading killer, despite the overall improvement in mortality of the patients treated with hypocholesterolemic drugs. One concept that has received much recent attention for the pathogenesis of atherosclerosis is the LDL-modification hypothesis, which postulates that atherosclerotic plaque resulted from the uptake of oxidized LDL by macrophages in the arterial wall followed by smooth muscle (SMC) migration and proliferation. In this respect, an understanding of the biochemical events, which impact on the oxidation stress SMC proliferation and its migration into the intima deserves to receive much attention. Inflammatory phenomena at sites of atherosclerotic plaques are increasingly thought to be major determinants of the progression and clinical outcome of atherosclerosis disease. Therefore, attention is being paid to systemic markers that may reflect the inflammatory activity in the plaques. Recently we found that haptoglobin (Hp), an acute phase protein elevated sharply during the infection and inflammation, was substantially accumulated in atherosclerotic lesions. Subsequently, we demonstrated that Hp was endogenously synthesized in macrophages, but not in SMC. Interestingly, for the first time we showed that SMC can express Hp mRNA in the presence of oxidized LDL with a dose-dependent manner. We also demonstrated in vitro that Hp is a highly potent antioxidant superior to probucol. Nevertheless, while the pathogenesis of atherosclerosis has been continuously explored, the Hp molecule that may protect against the progression of atherosclerosis has never been reported.