Tissue-type plasminogen activator is a potent mitogen for human aortic smooth muscle cells

• Published in: The Journal of biological chemistry 1994-01, Vol.269 (4), p.3076-3080
• Main Authors: HERBERT, J. M, LAMARCHE, I, PRABONNAUD, V, DOL, F, GAUTHIER, T
• Format: Article
• Language: English
• Subjects: alpha 1-Antitrypsin - pharmacology; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Biological and medical sciences; Cell Division - drug effects; Cell physiology; Cells, Cultured; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Genes, fos - drug effects; Genes, jun - drug effects; Humans; Inositol Phosphates - metabolism; Isoflurophate - pharmacology; Mitogens - pharmacology; Molecular and cellular biology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Pertussis Toxin; Phosphatidylinositols - metabolism; Plasminogen Activator Inhibitor 1 - pharmacology; Protease Inhibitors - pharmacology; Proto-Oncogenes - drug effects; Responses to growth factors, tumor promotors, other factors; RNA, Messenger - biosynthesis; Tissue Plasminogen Activator - pharmacology; Virulence Factors, Bordetella - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)42049-7

Tissue-type plasminogen activator (t-PA) is a potent and efficacious mitogen for growth-arrested cultured human aortic smooth muscle cells, stimulating an increase in cell number at 0.3-30 nM concentration. Double-chain t-PA is as efficient as single-chain t-PA in stimulating smooth muscle cell mitogenesis, whereas single-chain urokinase-type plasminogen activator (u-PA) or u-PA and plasmin or plasminogen are ineffective. Plasminogen activator inhibitor-1, Pefabloc-TPA, diisopropyl fluorophosphate or alpha 1-anti-trypsin inhibit the mitogenic effect of t-PA for smooth muscle cells in a dose-dependent manner, showing that it is dependent on the enzymatic activity. t-PA activated phosphoinositide turnover in smooth muscle cells through a pertussis toxin-insensitive pathway and stimulated proto-oncogene c-fos and c-jun mRNA levels. These findings indicate that t-PA stimulates vascular human smooth muscle cell proliferation and suggest for the first time that it may contribute to intimal smooth muscle cell proliferation after vascular injury as a result of angioplasty or vascular compromise during atherogenesis.