Carvedilol 단독 또는 Cyclosporine과의 병합투여가 배양된 백서 대동맥 혈관 평활근세포의 이동에 미치는 영향
Effect of Carvedilol Alone or with Cyclosporine on the Migration of Cultured Rat Vascular Smooth Muscle Cell
김명수, 조장환, 김혜진, 하헌주, 김유선, 박제현, 박기일,
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김명수 ( Kim Myoung-Soo )
연세대학교 대학원 의학과
조장환 ( Cho Jang-Hwan )
연세대학교 의과대학 외과학교실
김혜진 ( Kim Hae-Jin )
연세대학교 의과대학 외과학교실
하헌주 ( Ha Hun-Joo )
연세대학교 대학원 의학과
김유선 ( Kim Yu-Seun )
연세대학교 대학원 의학과
박제현 ( Park Je-Hyun )
연세대학교 대학원 의학과
박기일 ( Park Ki-Il )
연세대학교 대학원 의학과
KMID : 0371320010600010008
Abstract
Purpose: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which are triggered by endothelium-derived cytokines or growth factors, play a major role in the chronic transplant vasculopathy or vascular remodeling process after vascular injury. We have reported that carvedilol, a new anti-hypertensive agent, inhibits cytokine-triggered proliferation of cultured rat VSMCs. In this study, we investigate the effect of carvedilol on the migration of rat VSMCs.
Methods: Growth-arrested cultured VSMCs (passage 8∼11) from the aorta of rat (Sprague-Dawley) were used. Migration was measured using a microchemotaxis chamber with a polycarbonate membrane. Platelet derived growth factor (PDGF) or angiotensin-II (ANG-II) was used as a stimulator and was added into the lower well of the chamber. A density of 1×104 cells per well with carvedilol and/or cyclosporine A (CsA) was seeded into the upper well of chamber. Degree of migration was assessed by using the number of migrated cells per high power field of light microscopy.
Results: PDGF and ANG-II stimulated VSMC chemotaxis effectively. Carvedilol decreased PDGF-induced migration to 88.9 (±16.0)% and 37.4 (±10.5)% at 1μM and 10 μM, respectively. Carvedilol inhibited both PDGF and ANG-II induced chemotaxis in a concentration-dependent manner. The IC50 of carvedilol in PDGF and ANG-ll-induced VSMC migration was around 10μM. CsA (100 nM) neither significantly inhibited the migration of VSMC, regardless of the kinds of cytokines, nor affected the inhibitory activities of carvedilol. The pattern of inhibition in the group with a combined addition of carvedilol and CsA was very similar to that of carvedilol alone group, regardless of the kinds of cytokines.
Conclusion: We demonstrated that carvedilol alone or in the presence of CsA significantly inhibited the cytokine- induced migration of VSMC. These data indicate that carvedilol has a unique potential to reduce the development of chronic transplant vasculopathy when used with CsA in hypertensive renal transplant recipients.
키워드
혈관 평활근세포 이동
Cyclosporine;Carvedilol;Vascular smooth muscle cell;Migration;Cyclosporine;Carvedilol
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