Influence of Endothelin-1 on Cultured Vascular Smooth Muscle Cell Proliferation.
10.4070/kcj.1996.26.4.887
- Author:
Young Joo CHA
;
Cheol Ho KIM
- Publication Type:Original Article
- Keywords:
VSMC;
ET-1;
PDGF;
BQ123
- MeSH:
Aorta;
Atherosclerosis;
Cell Culture Techniques;
Cell Proliferation*;
DNA;
Eagles;
Endothelial Cells;
Endothelin-1*;
Intercellular Signaling Peptides and Proteins;
Muscle, Smooth, Vascular*;
Nitric Oxide Synthase
- From:Korean Circulation Journal
1996;26(4):887-893
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Proliferation of vascular smooth muscle cells(VSMC) is a critical event in the development of atherosclerosis. Endothelin-1(ET-1), a vasoconstrictor peptide produced by endothelial cells and VSMC, might play a role in vascular remodeling. To investigate the proposed 'mitogenic' potential of ET-1, we examined the effects of ET-1 on the proliferation if cultured porcine aortic VSMC and on the potential synergism with platelet-derived growth factor(PDGF). MATERIALS AND METHODS: VSMC were obtained from porcine aorta and cultured in Dulbecco's modified Eagle medium supplmented with 10% fetal bovine serum(FBS). VSMC grown subconfluently in 12-well plate were stimulated by ET-1, PDGF, and ET-1 & PDGF and DNA synthesis was determined as the uptake of 3H-thymidine into cell cultures. We also examined the effects of BQ123, a selective ETA receptor antagonist, and NG-methyl-L-arginine(NMLA), a nitric oxide synthase (NOS) inhibitor. RESULTS: ET-1 elicited a 2.5-fold increase of cultured VSMC DNA synthesis, comparing with basal medium, and PDGF elicited a 4.8-fold increase, whereas ET-1 and PDGF elicited a 8.8-fold increase, showing synergistic effect. Proliferative activity of ET-1 on VSMC was blocked(39%) by BQ123, however, the synergistic effect of ET-1 and PDGF was not blocked by BQ123. The synergistic effect of ET-1 and PDGF was increased when co-stimulated with NMLA. CONCLUSION: ET-1 is a co-mitogen for VSMC from porcine aorta, whose proliferative activity requires serum or other growth factors such as PDGF for its maximal activity. The proliferative activity of ET-1 is considered to be transduced partly by selective activation of the ETA receptor, however, the synergistic effect of of ET-1 and PDGF is to be stimulated by non-ETA receptor.
