Homocysteine as a risk factor for vascular disease - Enhanced collagen production and accumulation by smooth muscle cells

Homocysteine as a risk factor for vascular disease - Enhanced collagen production and accumulation by smooth muscle cells
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DOI:
10.1161/01.atv.17.10.2074
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发表时间:
1997-10-01
影响因子:
8.7
通讯作者:
Pezacka, EH
Pezacka, EH
中科院分区:
医学1区
文献类型:
--
作者:
Majors, A;Ehrhart, LA;Pezacka, EH

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血浆同型半胱氨酸水平升高是血管疾病的独立危险因素。然而,同型半胱氨酸促进动脉粥样硬化的病理机制尚不清楚。在同型半胱氨酸存在下培养的动脉平滑肌细胞生长到更高的密度,产生和积累的胶原蛋白水平显著高于对照组。同型半胱氨酸浓度低至50 μ mol/L时,细胞密度和胶原蛋白产量均显著增加。在同型半胱氨酸处理的培养中,细胞密度增加了43%。同型半胱氨酸以剂量依赖的方式增加胶原蛋白的产生。在高同型半胱氨酸血症患者中观察到的高浓度同型半胱氨酸处理平滑肌细胞的胶原合成率高达控制值的214%。同样,在同型半胱氨酸处理的培养中,细胞层中的胶原积累几乎增加了一倍。在同型半胱氨酸处理的培养物中添加水产养殖蛋白可以控制平滑肌细胞增殖和胶原生成的增加。这些结果表明了同型半胱氨酸致动脉粥样硬化的细胞机制,并为潜在的预防治疗提供了见解。
An increased plasma homocysteine level is an independent risk factor for vascular disease. However, the pathological mechanisms by which homocysteine promotes atherosclerosis are not yet clearly defined. Arterial smooth muscle cells cultured in the presence of homocysteine grew to a higher density and produced and accumulated collagen at levels significantly above control values. Homocysteine concentrations as low as 50 mu mol/L significantly increased both cell density and collagen production. Cell density increased by as much as 43% in homocysteine-treated cultures. Homocysteine increased collagen production in a dose-dependent manner. Smooth muscle cells treated with homocysteine at concentrations observed in patients with hyperhomocysteinemia had collagen synthesis rates as high as 214% of control values. Likewise, collagen accumulation in the cell layer was nearly doubled in homocysteine-treated cultures. Addition of aquacobalamin to homocysteine-treated cultures controlled the increase in smooth muscle cell proliferation and collagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential preventive treatment.