Inoue Ikuo
Fourth Department of Medicine, Saitama Medical School.
Nihon Rinsho. 2005 Apr;63(4):643-56.
The main pathological findings in atherosclerosis include abnormal reactions of neutrophils, lymphocytes and monocytes/macrophages, vascular smooth muscle cells and vascular endothelial cells, and the accumulation of cholesterol ester in the arterial wall. Therefore, investigating the effects of these abnormal reactions on the arterial wall may improve understanding of the mechanisms underlying atherosclerosis. Three types of peroxisome proliferator-activated receptors (PPARs): PPARalpha, PPARbeta/delta, and PPARgamma are expressed in endothelial cells. In endothelial cells, the ligands/activators for PPARalpha and PPARgamma increase Cu2+, Zn2+ -superoxide dismutase. In addition, the phorbol myristate acetate (PMA)-stimulated 22 kDa-subunit (p22phox) protein levels and 47 kDa-subunit (p47phox) protein levels in NADPH (superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (reduced form)) oxidase were decreased by treatment with PPARalpha and PPARgamma ligands/activators. Recently, we showed that the CLOCK: BMAL1 heterodimer regulates the PPARalpha gene via promoter of PPARalpha. Moreover, we report a patient with severe hypertriglyceridemia associated with anemia and hypoalbuminemia, in which the former may have caused the latter two conditions. This is the first reported case of abrupt onset of severe hypertriglyceridemia resulting in suppression of bone marrow and liver function. Here, based on recent studies including our own, we describe the relationships between risk factors for atherosclerosis, especially hyperlipidemia and PPARs and the molecular mechanisms that govern lipid metabolism in the arteries.
动脉粥样硬化的主要病理表现包括中性粒细胞、淋巴细胞和单核细胞/巨噬细胞、血管平滑肌细胞及血管内皮细胞的异常反应，以及胆固醇酯在动脉壁的蓄积。因此，研究这些异常反应对动脉壁的影响可能有助于增进对动脉粥样硬化潜在机制的理解。过氧化物酶体增殖物激活受体（PPAR）有三种类型：PPARα、PPARβ/δ和PPARγ，它们在内皮细胞中表达。在内皮细胞中，PPARα和PPARγ的配体/激活剂可增加铜离子、锌离子超氧化物歧化酶。此外，用PPARα和PPARγ配体/激活剂处理后，佛波酯（PMA）刺激的NADPH（超氧化物生成酶烟酰胺腺嘌呤二核苷酸磷酸（还原型））氧化酶中的22 kDa亚基（p22phox）蛋白水平和47 kDa亚基（p47phox）蛋白水平降低。最近，我们发现CLOCK:BMAL1异二聚体通过PPARα启动子调节PPARα基因。此外，我们报告了一例患有严重高甘油三酯血症并伴有贫血和低白蛋白血症的患者，前者可能导致了后两种情况。这是首次报道的严重高甘油三酯血症突然发作导致骨髓和肝功能受抑制的病例。在此，基于包括我们自己的研究在内的近期研究，我们描述动脉粥样硬化危险因素，尤其是高脂血症与PPARs之间的关系以及动脉中脂质代谢的分子机制。
