| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
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.
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