NOVEL CELLULAR ACTIVITIES FOR LOW-DENSITY-LIPOPROTEIN IN VASCULAR SMOOTH-MUSCLE CELLS
NOVEL CELLULAR ACTIVITIES FOR LOW-DENSITY-LIPOPROTEIN IN VASCULAR SMOOTH-MUSCLE CELLS
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DOI：
10.1161/01.hyp.15.6.704
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发表时间：
1990-06-01
期刊：
影响因子：
8.3
通讯作者：
VETTER, W
中科院分区：
文献类型：
--
作者：
SACHINIDIS, A;MENGDEN, T;VETTER, W
高脂血症和高血压在动脉粥样硬化的发病机制中起重要作用。为了探讨其潜在的细胞内机制，我们研究了正常血脂受试者不同浓度的低密度脂蛋白对大鼠血管平滑肌细胞和血管环内游离钙浓度、细胞内pH、DNA合成和血管张力的影响。低密度脂蛋白在1-15微克/毫升范围内可引起细胞内游离钙浓度的剂量依赖性升高和细胞内pH的双相改变。相似浓度的低密度脂蛋白可促进DNA合成。此外，累积加入1-15微克/毫升低密度脂蛋白可使大鼠胸主动脉环的收缩张力呈剂量依赖性增加。低密度脂蛋白引起的最大收缩反应约为40 mM KCl引起的收缩反应的70%。这些发现表明，低浓度低密度脂蛋白可能通过改变细胞内钙和细胞内pH而促进细胞增殖和血管收缩，从而参与心血管疾病的发病。
Hyperlipidemia and hypertension play important roles in the pathogenesis of atherosclerosis. To investigate the underlying intracellular mechanisms, we studied the effect of various concentrations of low density lipoprotein from normolipidemic subjects on concentrations of free intracellular calcium, intracellular pH, DNA synthesis, and vascular tone in vascular smooth muscle cells and rings from rat aortas. Low density lipoprotein in the range of 1-15 micrograms/ml induced a dose-dependent increase of concentration of free intracellular calcium and a biphasic change of the intracellular pH. Similar concentrations of low density lipoprotein led to an enhanced DNA synthesis. Furthermore, cumulative addition of 1-15 micrograms/ml low density lipoprotein produced a dose-dependent increase in contractile tension of thoracic aortic rings from rats. The maximal low density lipoprotein-induced contractile response was approximately 70% of that induced by 40 mM KCl. These findings indicate that low concentrations of low density lipoprotein occurring, for example, in the extravascular fluid might contribute to the pathogenesis of cardiovascular diseases by enhancing cell proliferation and vasoconstriction by changing intracellular calcium and intracellular pH.