Hypercholesterolemia induces regression in neointimal thickening due to apoptosis of vascular smooth muscle cells in the hamster endothelial injury model
Hypercholesterolemia induces regression in neointimal thickening due to apoptosis of vascular smooth muscle cells in the hamster endothelial injury model
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DOI：
10.1016/s0008-6363(01)00467-9
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发表时间：
2002-02-01
影响因子：
10.8
通讯作者：
Umemura, K
中科院分区：
文献类型：
--
作者：
Matsuda, A;Suzuki, Y;Umemura, K
目的：高胆固醇血症是动脉粥样硬化的主要危险因素。尽管基质金属蛋白酶可能在斑块破裂中起关键作用，但胆固醇及其氧化物诱导的血管平滑肌细胞（VSMCs）凋亡也可能导致斑块的不稳定和破裂。因此，我们研究了高胆固醇血症在仓鼠股动脉内皮损伤后血管重构中的作用。方法：利用光敏染料虎红与绿色光的光化学反应损伤内皮细胞。本实验室常规采用光化学反应在实验动物中产生无机械拉伸的内皮损伤。结果如下：在正常胆固醇血症仓鼠（NCH）中，内皮损伤后3周观察期内新生内膜增厚逐渐进展。在高胆固醇血症仓鼠（HCH），新生内膜增厚逐渐进展，直到第二周后内皮损伤。相反，在第三周，新生内膜增厚消退，比第二周更薄。HCH和NCH对VSMCS体内增殖的影响无显著性差异。内皮损伤后2 ~ 4周，HCH组新生内膜和中膜可见凋亡细胞，而NCH组未见凋亡细胞。内皮损伤后2周，HCH组TUNEL阳性VSMC数量明显高于NCH组（新生内膜：1.2 +/- 103 vs. 0.3 +/-0.1%，P < 0.05，中膜：2.9 +/- 0.6 vs. 0.6 +/-0.2%，P < 0.01）。胆固醇存款。油红O染色可见HCH的新生内膜或中膜区，而NCH则无。结论：提示高胆固醇血症合并内皮损伤可诱导VSMC凋亡，继而使内膜增厚消退，进一步高胆固醇血症可能通过VSMC凋亡诱导斑块破裂。(C)2002 Elsevier Science B. V.保留所有权利。
Objective: Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Although matrix metalloproteinase may play a key role in plaque rupture, apoptosis of vascular smooth muscle cells (VSMCs), which is induced by cholesterol and its oxides may also contribute to instability and rupture of plaque, Thus, we investigated the roles of hypercholesterolemia in vascular remodeling following endothelial injury in the hamster femoral artery. Methods: The endothelium was injured by photochemical reaction between green light and the photosensitizer dye, Rose Bengal. Photochemical reaction is routinely used in our laboratory to produce endothelial injury without mechanical stretching in experimental animals. Results: In normocholesterolemic hamsters (NCH), neointimal thickening gradually progressed within a 3-week observation period after endothelial injury. In hypercholesterolemic hamsters (HCH), neointimal thickening gradually progressed until the second week after endothelial injury. In contrast, at the third week neointimal thickening regressed and was thinner than that at the second week. There was no significant difference in in vivo proliferation of VSMCS detected by in vivo BrdU uptake between HCH and NCH. Apoptotic cells in the neointima and the media were observed in HCH from 2 to 4 week's after endothelial injury, but not in NCH. At 2 weeks after endothelial injury, the numbers of TUNEL-positive VSMCs in HCH were significantly higher than those in NCH (neointima; 1.2 +/- 103 vs. 0.3 +/- 0.1%, P < 0.05 , media; 2.9 +/- 0.6 vs. 0.6 +/- 0.2%, P < 0.01). Cholesterol deposit. which is detected by oil red O staining was observed in a neointimal or medial area in HCH, but not in NCH. Conclusions: These findings suggest that hypercholesterolemia with endothelial injury may, induce VSMC apoptosis, followed by the regression of neointimal thickening, further hypercholesteremia might play a role in inducing plaque rupture through apoptosis of VSMC. (C) 2002 Elsevier Science B.V. All rights reserved.