Proliferation and migration of vascular smooth muscle cell induced by novel physiologically active phospholipid

动脉粥样硬化与心脑血管疾病的发病机制有关。在这项研究中，我们研究了溶血磷脂酸(LPA)，一种生理活性磷脂，是否在动脉粥样硬化的发生和发展中发挥重要作用的可能性。用酶消化法分离自发性高血压大鼠(SHR)和Wistar京都系大鼠(WKY)的胸主动脉血管平滑肌细胞(VSMC)，并比较它们对LPA的增殖反应。与WKY的VSMC相比，SHR的VSMC在LPA刺激后4天的细胞数显著高于WKY的VSMC。LPA对VSMC的浓度-效应曲线比WKY的VSMC的浓度-效应曲线左移；SHR的VSMC的最大值高于WKY的VSMC，而EC；为了测量溶血磷脂酶D的活性，将大鼠血浆与放射性标记的溶血磷脂酰胆碱(1-Palmitoyl)在37ﾟC孵育不同时间，提取血浆中的脂质后测定生成的LPA。结果表明，溶血磷脂酶D活性具有年龄依赖性，两种品系的溶血磷脂酶D活性无显著差异，提示SHR的VSMC比WKY的VSMC具有更高密度的LPA受体，这可能参与了动脉粥样硬化的形成。另外，自发性高血压大鼠VSMC上LPA受体激活的信号转导通路可能与WKY大鼠VSMC上LPA激活的信号转导通路不同。

Atherosclerosis is relevant to pathogenesis of diseases of heart and brain vessels. In this study, we examined a possibility whether lysophosphatidic acid (LPA), a physiologically active phospholipid, play an important role in induction and development of atherosclerosis. Vascular smooth muscle cell (VSMC) was isolated by enzyme digestion of thoracic aotra of spontaneously hypertensive rat (SHR) and Wistar Kyoto strain of rat (WKY), and thier proliferative responses to LPA were compared. VSMC from SHR was found to incorporate more [^3H] thymidine into DNA in comparison with that from WKY,when these cells were cultured in the presence of LPA.In addition, the cell number of VSMC from SHR 4 days after stimulation with LPA was significantly higher than that from WKY.Concentration-response curves of LPA effects on VSMC from SHR were shifted to the left as compared with those on VSMC from WKY ; the maximal values obtained with VSMC from SHR became higher, whereas the EC_<50> values were lower.To measure the activity of lysophospholipase D,rat plasma was incubated with radiolabeled lysophosphatidylcholine (1-palmitoyl) at 37ﾟC for various times, and LPA generated was quantified after extraction of lipids from the plasma. Results show that the lysophospholipase D activity was age-indepndent, and that there was no significant difference between the activities in the plasma of both strains.Taken altogether, we suggested that VSMC from SHR has LPA receptors at a higher density than VSMC from WKY,which may be involved in induction of atherosclerosis. Alternatively, the signal transduction pathway triggered by LPA receptor on VSMC from SHR might be different from that stimulated with LPA in VSMC from WKY.