EPIDERMAL GROWTH-FACTOR RESPONSIVENESS IN SMOOTH-MUSCLE CELLS FROM HYPERTENSIVE AND NORMOTENSIVE RATS
EPIDERMAL GROWTH-FACTOR RESPONSIVENESS IN SMOOTH-MUSCLE CELLS FROM HYPERTENSIVE AND NORMOTENSIVE RATS
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DOI：
10.1161/01.hyp.13.4.295
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发表时间：
1989-04-01
期刊：
影响因子：
8.3
通讯作者：
BUHLER, FR
中科院分区：
文献类型：
--
作者：
SCOTTBURDEN, T;RESINK, TJ;BUHLER, FR
自发性高血压大鼠（SHR）的主动脉平滑肌细胞在培养中表现出不适当的增殖特性，这表明对血清有丝分裂原或生长因子的反应发生了改变。本研究比较了SHR和血压正常的Wistar-Kyoto（WKY）大鼠血管平滑肌细胞对生长因子的增殖和功能反应。特别关注的是这些血管平滑肌细胞与表皮生长因子的相互作用。当细胞在血清（10%和0.5%）存在下培养时，观察到SHR（与WKY大鼠相比）血管平滑肌细胞的生长速率增加，但在无血清条件下则不然。另外，低血清浓度（0.5%）的存在是表皮生长因子引起增殖反应所必需的，因此SHR的平滑肌细胞显示出增加（与WKY大鼠相比）。增速[125 I]表皮生长因子与完整平滑肌细胞的饱和结合表明SHR衍生细胞中受体密度增加了两倍（p < 0.001 vs. WKY大鼠），而对生长因子的亲和力没有改变。从SHR衍生的细胞也表现出更大的功能性反应表皮生长因子相比，平滑肌细胞从WKY大鼠的S6激酶激活，磷酸肌醇催化剂，细胞内pH值升高，DNA合成（核标记）的扩增证明。我们的结论是，SHR衍生的平滑肌细胞对表皮生长因子的反应性增加可能有助于血管平滑肌生长和张力的改变，这可能是高血压和动脉粥样硬化发病机制的基础。
Aortic smooth muscle cells from spontaneously hypertensive rats (SHR) exhibit inappropriate proliferation characteristics in culture that suggest a modified repsonse to serum mitogens or growth factors. The present study compares vascular smooth muscle cells from SHR and normotensive Wistar-Kyoto (WKY) rats with respect to their proliferative and function response to growth factors. Specific attention was focused on the interaction of these vascular smooth muscle cells with epidermal growth factor. An increased growth rate of vascular smooth muscle cells from SHR (vs. WKY rats) was observed when cells were cultured in the presence of serum (10% and 0.5%), but not under serum-free conditions. The additional presence of low serum concentrations (0.5%) was required for epidermal growth factor to elicit a proliferative response, whereupon smooth muscle cells from SHR displayed an increased (vs. WKY rats). growth rate. Saturation binding of [125I]epidermal growth factor to intact smooth muscle cells indicated a twofold increase in receptor density in SHR-derived cells (p < 0.001 vs. WKY rats) without an alteration in affinity for the growth factor. Cells derived from SHR also exhibited greater functional responsiveness to epidermal growth factor when compared with smooth muscle cells from WKY rats as evidenced by amplifications of both S6 kinase activation, phosphoinositide catabolism, elevation of intracellular pH, and DNA synthesis (nuclear labeling). We conclude that increased responsiveness of SHR-derived smooth muscle cells to epidermal growth factor could contribute to alterations in vascular smooth muscle growth and tone that may be fundamental to the pathogenesis of hypertension and atherosclerosis.