Effect of natriuretic peptide family on the oxidized LDL-induced migration of human coronary artery smooth muscle cells
Effect of natriuretic peptide family on the oxidized LDL-induced migration of human coronary artery smooth muscle cells
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DOI：
10.1161/01.res.81.4.585
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发表时间：
1997-10-01
影响因子：
20.1
通讯作者：
Yoshikawa, J
中科院分区：
文献类型：
--
作者：
Kohno, M;Yokokawa, K;Yoshikawa, J
内膜平滑肌细胞（SMCs）向内膜的迁移被认为是动脉粥样硬化病变中内膜增厚的重要过程。本研究通过Boyden's chamber法研究了一种新型内皮来源的松弛肽c型利钠肽（CNP）对氧化低密度脂蛋白（LDL）诱导的培养人冠状动脉SMCs迁移的可能影响。比较CNP与心房利钠肽和脑利钠肽（分别为ANP和BNP）的作用。氧化LDL以浓度依赖性的方式刺激SMC迁移在20和200 μ g/mL之间。这种刺激在本质上是趋化的，但不是趋化动力学的。相比之下，天然LDL无显著活性。CNP-22在10（-9）和10(-6)mol/L之间以浓度依赖性的方式明显抑制200 μ g/mL氧化LDL刺激的SMC迁移。ANP-(1-28)和BNP-32在10（-7）和10(-6)mol/L浓度下也能抑制氧化ldl诱导的SMC迁移，但其作用弱于CNP-22。这些利钠肽的这种抑制作用与cGMP细胞水平的增加是平行的。氧化ldl诱导的迁移被稳定的cGMP类似物，8-溴-cGMP，或胞质鸟苷酸环化酶激活剂硝普钠显著抑制。这些利钠肽在没有或存在氧化LDL的情况下都不抑制细胞粘附。这些数据表明，氧化LDL刺激人冠状动脉SMCs的迁移，而利钠肽，特别是CNP，通过cgmp依赖的过程，至少部分地抑制了这种受刺激的SMC迁移。结合发现氧化LDL存在于内膜中，CNP可能在高胆固醇血症引起的冠状动脉粥样硬化的内膜增厚过程中发挥局部抗迁移因子的作用。
The migration of medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in atherosclerotic lesions. The present study examined the possible effect of a novel endothelium-derived relaxing peptide, C-type natriuretic peptide (CNP), on oxidized low-density lipoprotein (LDL)-induced migration of cultured human coronary artery SMCs by the Boyden's chamber method. The effect of CNP was compared with that of atrial and brain natriuretic peptides (ANP and BNP, respectively). Oxidized LDL stimulates SMC migration in a concentration-dependent manner between 20 and 200 mu g/mL. This stimulation was chemotactic in nature but was not chemokinetic. By contrast, native LDL was without significant activity. CNP-22 clearly inhibited SMC migration stimulated with 200 mu g/mL oxidized LDL in a concentration-dependent manner between 10(-9) and 10(-6) mol/L. ANP-(1-28) and BNP-32 also inhibited oxidized LDL-induced SMC migration at concentrations of 10(-7) and 10(-6) mol/L, but these effects were weaker than the effect of CNP-22. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. Oxidized LDL-induced migration was significantly inhibited by a stable analogue of cGMP, 8-bromo-cGMP, or an activator of the cytosolic guanylate cyclase, sodium nitroprusside. These natriuretic peptides did not suppress the cell adhesion either in the absence or presence of oxidized LDL. These data indicate that oxidized LDL stimulates migration of human coronary artery SMCs and that natriuretic peptides, especially CNP, inhibit this stimulated SMC migration, at least in part, through a cGMP-dependent process. Taken together with the finding that oxidized LDL is present in the intima, CNP may play a role as a local antimigration factor during the process of intimal thickening in hypercholesterolemia-induced coronary atherosclerosis.