Effect of Natriuretic Peptide Family on the Oxidized LDL-Induced Migration of Human Coronary Artery Smooth Muscle Cells

• Published in: Circulation research Vol. 81; no. 4; pp. 585 - 590
• Main Authors: Kohno, Masakazu, Yokokawa, Koji, Yasunari, Kenichi, Kano, Hiroaki, Minami, Mieko, Ueda, Makiko, Yoshikawa, Junichi
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.10.1997; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Movement - drug effects; Cells, Cultured; Coronary Vessels - cytology; Coronary Vessels - drug effects; Coronary Vessels - physiology; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Cyclic GMP - pharmacology; Humans; Lipoproteins, LDL - pharmacology; Medical sciences; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Natriuretic Agents - pharmacology; Natriuretic Peptide, C-Type; Nitric Oxide - biosynthesis; Nitroprusside - pharmacology; Peptide Fragments - pharmacology; Proteins - pharmacology; Vascular disease; Human; Lipoprotein LDL; Migration; Coronary artery; Atherosclerosis; Cardiovascular disease; Smooth muscle; 3',5'-GMP; C type natriuretic peptide; Myocyte
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.81.4.585

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 micro 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 micro g/mL oxidized LDL in a concentration-dependent manner between 10 sup -9 and 10 sup -6 mol/L. ANP-(1-28) and BNP-32 also inhibited oxidized LDL-induced SMC migration at concentrations of 10 sup -7 and 10 sup -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. (Circ Res. 1997;81:585-590.)