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(Hypertension. 2000;35:971.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Effects of Cardiac Natriuretic Peptides on Oxidized Low-Density Lipoprotein– and Lysophosphatidylcholine-Induced Human Mesangial Cell Migration

Masakazu Kohno; Kenichi Yasunari; Kensaku Maeda; Hiroaki Kano; Mieko Minami; Takao Hanehira; Junichi Yoshikawa

From The First Department of Internal Medicine, Osaka City University Medical School, Abeno-ku, Osaka, Japan.

Correspondence to Masakazu Kohno, MD, The First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545-8586, Japan.

Abstract—The objectives of the present study were (1) to determine whether oxidized LDL and lysophosphatidylcholine (lyso-PtdCho), a major phospholipid component of oxidized LDL, stimulate the migration of cultured human mesangial cells and (2) to investigate the possible effects on mesangial cell migration of the cardiac natriuretic peptides atrial and brain natriuretic peptide (ANP and BNP). Oxidized LDL (10 and 100 µg/mL) and lyso-PtdCho (10^-7 to 10^-5 mol/L) stimulated migration in a concentration-dependent manner. In contrast, the effects of native LDL and phosphatidylcholine were modest or nonexistent. Protein kinase C (PKC) inhibitor and downregulation of PKC activity by phorbol ester inhibited oxidized LDL– and lyso-PtdCho–induced migration. Human ANP(1-28) and human BNP-32 significantly inhibited oxidized LDL– and lyso-PtdCho–induced migration in a concentration-dependent manner. C-ANF {des-[Glu¹⁸,Ser¹⁹,Gly²⁰,Leu²¹,Gly²²]ANP(4-23)}, a specific ligand for ANP clearance receptors, could not inhibit oxidized LDL– and lyso-PtdCho–induced migration. Inhibition by ANP and BNP of lyso-PtdCho–induced migration was paralleled by an increase in the cellular level of GMP. Oxidized LDL– and lyso-PtdCho–induced migrations were inhibited by 8-bromo-cGMP. The results suggest that oxidized LDL and lyso-PtdCho stimulate the migration of human mesangial cells, at least in part, through a PKC-dependent process and that ANP and BNP inhibit this stimulated migration, probably through a cGMP-dependent process.

Key Words: lysophosphatidylcholines • lipoproteins • atrial natriuretic factors • glomerular mesangium • natriuretic peptide, brain

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