1,25-DIHYDROXYVITAMIN-D3 AND RAT VASCULAR SMOOTH-MUSCLE CELL-GROWTH
1,25-DIHYDROXYVITAMIN-D3 AND RAT VASCULAR SMOOTH-MUSCLE CELL-GROWTH
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DOI：
10.1161/01.hyp.13.6.954
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发表时间：
1989-06-01
期刊：
影响因子：
8.3
通讯作者：
OOI, BS
中科院分区：
文献类型：
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作者：
MACCARTHY, EP;YAMASHITA, W;OOI, BS
最近几个实验室的研究表明，高血压时1，25-二羟基维生素D3[1，25(OH)2D3]代谢紊乱。虽然这些扰动可能通过对钙代谢的作用而对血压产生影响，但这种维生素D代谢产物可能对血管平滑肌细胞(VSMC)的生理有直接影响。为了验证这一点，我们研究了1，25(OH)2D3对VSMC生长的影响，发现该物质抑制VSMC[~3H]胸腺嘧啶核苷的摄取，而且这种维生素D代谢产物也抑制了表皮生长因子(EGF)对VSMC增殖的刺激作用。这种物质的存在似乎是其对VSMC生长的作用所必需的，因为用维生素D代谢物预处理长达72小时，然后清洗该物质的细胞正常生长，并对EGF有反应。研究还确定了1，25(OH)2D3是否对VSMC上EGF受体的功能有影响。用~(125)I标记EGF的实验表明，该配体与VSMC的结合在未经处理和1，25(OH)2D3处理的情况下没有差异，这表明维生素D代谢产物对VSMC生长的影响(当暴露于EGF时)不是通过改变EGF受体功能来实现的。这些研究结果对高血压和动脉粥样硬化等血管疾病的发病机制具有重要意义。
Recent studies from several laboratories have shown perturbations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism in hypertension. While these perturbations may exert their effect on blood pressure via their actions on calcium metabolism, it is possible that this vitamin D metabolite may have direct effects on vascular smooth muscle cell (VSMC) physiology. To examine this, we studied the effect of 1,25(OH)2D3 on VSMC growth and found that this substance suppressed VSMC [3H]thymidine uptake; furthermore, this vitamin D metabolite also suppressed the stimulatory effect of epidermal growth factor (EGF) on VSMC proliferation. The concomitant presence of this substance appeared to be required for its action on VSMC growth since cells pretreated with the vitamin D metabolite for up to 72 hours and then washed of the substance grew normally and responded to EGF. Studies were also done to determine if 1,25(OH)2D3 had any effect on the function of EGF receptors on VSMC. Experiments using Iodine-125-labeled EGF showed no differences in the binding of this ligand to VSMC, either untreated or treated with 1,25(OH)2D3, which indicates the effect of the vitamin D metabolite on VSMC growth (when exposed to EGF) was not mediated by an alteration of EGF receptor function. The results of these studies have implications for the pathogenesis of vascular diseases such as hypertension and atherosclerosis.