Effect of Carvedilol on Human Vascular Smooth Muscle Cell Proliferation and Its Signal Transduction.
- Author:
Jehyun PARK
1
;
Hunjoo HA
;
Jae Won OH
;
Myoung Soo KIM
;
Jiyeon SEO
;
Hae Jin KIM
;
Kiil PARK
;
Yu Seun KIM
Author Information
1. Department of Surgery and The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea. yukim@yumc.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Carvedilol;
Vascular;
Smooth muscle cell;
Reactive oxygen;
Mitogen-activated protein kinases
- MeSH:
Blotting, Western;
Cell Proliferation*;
Culture Media, Serum-Free;
Humans*;
Mitogen-Activated Protein Kinases;
Muscle, Smooth, Vascular*;
Myocytes, Smooth Muscle;
p38 Mitogen-Activated Protein Kinases;
Platelet-Derived Growth Factor;
Reactive Oxygen Species;
Sclerosis;
Signal Transduction*;
Vascular System Injuries
- From:Journal of the Korean Society for Vascular Surgery
2002;18(1):15-22
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Vascular smooth muscle cells (VSMCs) migration and proliferation play important roles in transplant vascular sclerosis and restenosis after balloon vascular injury. The anti-proliferative and anti- migratory effects of carvedilol (CA), a unique alpha- and beta-blocking anti-hypertensive drug, on the VSMCs were confirmed previously. Since reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) family play important roles in proliferation of VSMCs, the present study examined the effects of CA on intracellular ROS generation, activation of ERK1/2 and p38 MAPK, and proliferation of VSMCs cultured under platelet derived growth factor (PDGF). METHODS: Human VSMCs obtained from ATCC were cultured with RPMI-1640 containing 10% fetal bovine serum. Near confluent VSMCs were incubated with serum-free media for 48 hours to arrest and synchronize the cell growth. CA was administered 1 hour before the addition of PDGF. 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein (DCF)-sensitive intracellular ROS was detected by FACS. Activations of ERK1/2 and p38 MAPK were measured by Western blot analysis. Proliferation of VSMCs was assessed by [3H]-thymidine incorporation. RESULTS: PDGF at 10 ng/ml, which induced human VSMCs proliferation, rapidly increased intracellular ROS by 1.6-fold (P<0.01), ERK1/2 activation by 2.1-fold (P<0.01), and p38 MAPK activation by 1.9-fold (P<0.01), respectively, as compared to the control. CA 1 and 10muM effectively inhibited PDGF-induced human VSMCs proliferation. CA also effectively inhibited PDGF-induced intracellular ROS generation as well as ERK1/2 and P38 MAPK activation. CONCLUSION: The present study suggests that CA inhibits PDGF-induced human VSMCs proliferation, possibly by inhibiting intracellular ROS generation and activation of ERK1/2 and p38 MAPK.
