Mitsumata M, Fishel R S, Nerem R M, Alexander R W, Berk B C
School of Mechanical Engineering, Georgia Institute of Technology, Atlanta 30332-0405.
Am J Physiol. 1993 Jul;265(1 Pt 2):H3-8. doi: 10.1152/ajpheart.1993.265.1.H3.
Fluid flow and the associated shear stress play a critical role in vascular growth and remodeling. Recent data suggest that increased endothelial cell expression of platelet-derived growth factor (PDGF) A- and B-chain by flow may participate in these events. In the present study, we examined the mechanism for flow-induced PDGF expression, focusing on protein kinase C (PKC). Bovine aortic endothelial cells were exposed to flow (shear stress = 30 dyn/cm2) in a parallel-plate flow chamber. Increases in PDGF B-chain, but not PDGF A-chain, were observed within 3 h, maximal within 6 h (13-fold increase), and sustained for 24 h. PKC appeared to be involved because phorbol 12-myristate 13-acetate induced PDGF B-chain mRNA. Activation of PKC alone, however, was insufficient to induce PDGF mRNA because the selective PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, did not induce PDGF expression. A PKC-independent pathway was suggested by the fact that inhibition of PKC (downregulation with phorbol 12,13-dibutyrate or exposure to staurosporine) failed to block PMA or flow-induced PDGF B-chain expression. These results demonstrate flow-induced PDGF B-chain expression in endothelial cells that appears to be mediated, in part, by a PKC-independent pathway.
流体流动及相关的剪切应力在血管生长和重塑过程中起着关键作用。最近的数据表明，流动增加内皮细胞血小板衍生生长因子（PDGF）A链和B链的表达可能参与这些过程。在本研究中，我们研究了流动诱导PDGF表达的机制，重点关注蛋白激酶C（PKC）。将牛主动脉内皮细胞置于平行平板流动腔中暴露于流动（剪切应力 = 30达因/平方厘米）。在3小时内观察到PDGF B链增加，但PDGF A链未增加，6小时内达到最大值（增加13倍），并持续24小时。PKC似乎参与其中，因为佛波醇12-肉豆蔻酸酯13-乙酸酯可诱导PDGF B链mRNA。然而，单独激活PKC不足以诱导PDGF mRNA，因为选择性PKC激活剂1-油酰基-2-乙酰基-sn-甘油不能诱导PDGF表达。PKC抑制（用佛波醇12,13-二丁酸酯下调或暴露于星形孢菌素）未能阻断佛波酯或流动诱导的PDGF B链表达，这表明存在一条不依赖PKC 的途径。这些结果表明，流动诱导内皮细胞中PDGF B链的表达，这似乎部分是由一条不依赖PKC的途径介导的。
