Role of chylomicron remnants in vascular remodeling

所有形式的经皮冠状动脉介入治疗都会对血管造成损伤。动脉对损伤的反应是长期预后的基础。血管成形术时，血栓、炎症、内膜和内侧夹层以及动脉壁的弹性回缩会导致新生内膜的形成。乳糜粒残留物是餐后高脂血症的主要脂蛋白，被认为是致动脉粥样硬化的脂蛋白。然而，乳糜管残留物促进动脉粥样硬化的机制还不完全清楚。在这里，我们研究了乳糜管残留物对内皮细胞和平滑肌细胞的影响。我们从饲喂蛋液的大鼠的淋巴中制备乳杆菌微粒，并从注射乳糜微粒的功能性肝切除大鼠的血浆中获得乳杆菌微粒残留物。首先，我们研究了乳糜管残留对人脐静脉内皮细胞(HUVEC)的影响。乳清蛋白残留物激活Caspase-3活性和…更多地诱导HUVECs凋亡，呈剂量依赖关系。接下来，我们研究了乳糜管残留物对培养的血管平滑肌细胞单核细胞趋化蛋白-1(MCP-1)表达的影响。单核细胞趋化蛋白-1(MCP-1)是一种趋化因子，可刺激单核细胞迁移，在动脉粥样硬化的发生发展中起关键作用。乳清蛋白残留物处理VSMC后，MCP-1mRNA和蛋白表达显著增加，并呈时间和剂量依赖关系。此外，乳糜管残留物还激活了p38丝裂原活化蛋白激酶(MAPK)和细胞外信号调节激酶(ERK1/2)。P38 MAPK抑制剂SB203580和SB202190可剂量依赖性地抑制乳糜管残留物诱导的MCP-1mRNA和蛋白表达，而MAPK抑制剂(PD98059)对此无影响。乳糜粒残留物诱导的MCP-1分泌比乳糜粒、氧化型低密度脂蛋白或溶血磷脂酰胆碱诱导的要明显得多。Ohylomicron残留物可能通过诱导内皮细胞凋亡和刺激VSMCs表达MCP-1而加重动脉粥样硬化。较少

All forms of percutaneous coronary intervention confer injury on the vessel. The arterial response to that injury is the basis for long-term outcome. Neointima forms in response to thrombus, inflammation, intimal and medial dissections, and elastic recoil of the arterial wall when augioplasry was performed. Chylomicron remnants, major lipoproteins at postprandial hyperlipidemia, is considered to be proatherogenic lipoproteins. However, the mechanisms by which chylomicron remnants enhance atherosclerosis have not been fully understood. Here, we examined the effect of chylomicron remnants on endothelial cells and smooth muscle cells. We prepared chylomicrons from the lymph of the rats which were fed with egg solution and obtained chylomicron remnants from the plasma of functionally hepatectomized rats injected with chylomicrons. First, we examined the effect of chylomicron remnants on human umbilical vein endomelial cells (HUVECs). Chylomicron remnants activated caspase-3 activity and in … More duced apoptosis of HUVECs in a dose dependent manner. Next, we investigated the effect of chylomicron remnants on monocyte chemoattractant protein-1 (MCP-1) expression in cultured vascular smooth muscle cells (VSMCs). MCP-1 is a chemokine, which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. Treatment of VSMC with chylomicron remnants significantly increased the expression of MCP-1 mRNA and protein in a time-and dose-dependent manner. Furthermore, chylomicron remnants activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2). Pretreatment of VSMCs with p38 MAPK inhibitors,SB203580 and SB202190, dose-dependently inhibited chylomicron remnants-induced MCP-1 mRNA and protein expression,whereas a MAPK kinase inhibitor (PD98059) had no effect on these responses. Chylomicron remnants-induced MCP-1 secretion into the media was much more pronounced than those induced by chylomicrons, oxidized low-density lipoproteins, or lysophosphatidylcholine. Ohylomicron remnants may exacerbate atherosclerosis by inducing endothelial cell apoptosis and stimulating MCP-1 expression in VSMCs. Less