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，我们探讨了溶血磷脂酸（LPA）作为一种具有生理活性的磷脂，是否在动脉粥样硬化的诱导和发展中发挥重要作用。采用酶切法从自发性高血压大鼠（SHR）和Wistar Kyoto大鼠（WKY）胸主动脉分离血管平滑肌细胞（VSMC），比较其对LPA的增殖反应。当这些细胞在LPA存在下培养时，发现来自SHR的VSMC比来自WKY的VSMC在DNA中加入了更多的[^3H]胸腺嘧啶。此外，LPA刺激4 d后SHR组VSMC细胞数量显著高于WKY组。与WKY VSMC相比，LPA对SHR VSMC影响的浓度-响应曲线向左偏移；从SHR获得的VSMC最大值越来越高，而EC_<50>的值越来越低。为了测定溶血磷脂酶D的活性，用放射性标记的溶血磷脂酰胆碱（1-棕榈酰）在37℃的温度下孵育大鼠血浆，并定量提取血浆脂质后产生的LPA。结果表明，溶血磷脂酶D活性与年龄无关，两菌株血浆中溶血磷脂酶D活性无显著差异。综上所述，我们认为来自SHR的VSMC比来自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诱导。或者，LPA受体在SHR的VSMC上触发的信号转导途径可能与LPA在WKY的VSMC上刺激的信号转导途径不同。

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.