Effect of Carvedilol Alone or with Cyclosporine on the Proliferation of Rat Vascular Smooth Muscle Cell.
- Author:
Myoung Soo KIM
1
;
Yu Seun KIM
;
Hunjoo HA
;
Jehyun PARK
;
Haejin KIM
;
Kiil PARK
Author Information
1. Department of Surgery, Yonsei University College of Medicine, Korea. yukim@yumc.yonsei.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Carvedilol;
Vascular smooth muscle cell;
Proliferation
- MeSH:
Allografts;
Animals;
Aorta;
Cell Culture Techniques;
Culture Techniques;
Cyclosporine*;
Cytokines;
Endothelin-1;
Humans;
Inhibitory Concentration 50;
Intercellular Signaling Peptides and Proteins;
Muscle, Smooth, Vascular*;
Platelet-Derived Growth Factor;
Rats*;
Sclerosis;
Transplantation;
Vascular System Injuries
- From:The Journal of the Korean Society for Transplantation
2000;14(1):1-8
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Typical pathologic lesions of chronic allograft rejection or transplant vascular sclerosis are similar to arteriosclerotic vascular lesion of non-transplant patients, or vascular remodeling process after vascular injury. Abnormal and excess proliferation of vascular smooth muscle cells (VSMC) which are triggered by endothelium-derived cytokines or growth factors, play a major role during these process. Effective prophylactic or therapeutic strategies against chronic rejection or transplant vasculopathy is not yet clearly established. Recent in vitro cell culture study showed that carvedilol, a novel antihypertensive agent has the significant inhibitory activities against the proliferation of VSMC. METHODS: Using in vitro VSMC culture techniques, we measured anti-proliferative activity of carvedilol alone, or in combination of cyclosporine, a basic immunosuppressive agent for transplantation. Growth-arrested early passage (3-5) cultured VSMC from the aorta of rat (Sprague-Dawley) were exposed to platelet derived growth factor (PDGF), endothelin-l, or antiotensin-ll, respectively. Carvedilol and/or cyclosporine was added as inhibitors. Proliferation was assessed by incorporated [(3)H]-thymidine activity. RESULTS: PDGF stimulated mitogenesis most effectively. Carvedilol inhibited mitogenesis in dose-dependent manner in the presence of PDGF(10ng/ml). Compared to control, proliferation was significantly decreased to 60.3 (+/-10.4)% and 18.3 (+/- 5.9)% in the presence of 1 micro M and 10 micro M of carvidilol, respectively (p<0.05, each). Carvedilol also produced significant concentration-dependent inhibitory activities against VSMC stimulated by endothelin-1 (10 nM) and angiotensin-II (100 nM). The IC50 of carvedilol in PDGF-, endothelin-l, and angiotensin-ll-stimulated VSMC were 1-10 micro M. Cyclosporine (100 nM) did not show significant inhibition of VSMC regardless of the kinds of cytokines. However, combined addition of carvedilol and cyclosporine produced significant VSMC inhibition. The pattern of inhibition in c very similar with that of carvedilol alone group regardless of the kinds of cytokines. CONCLUSION: We demonstrated that carvedilol significantly inhibited the proliferation of VSMC regardless of the kind of cytokines, and even under the presence of cyclosporine in VSMC cultures. These indicated that carvedilol has the unique potential to reduce the development of transplant vasculopathy when used with cyclosporine in hypertensive renal transplant recipients.
