Resistin contributes to neointimal formation via oxidative stress after vascular injury.
Resistin may play a major potential role in vascular remodelling and may contribute to atherogenesis. However, the role of VSMC (vascular smooth muscle cell)-derived resistin in neointimal formation is not well understood. We hypothesize that endogenous resistin derived from VSMCs may contribute to neointimal formation after vascular injury. VSMCs from thoracic aorta of adult Wistar rats were cultured. The carotid artery from adult Wistar rats was injured by balloon catheter. Resistin significantly increased migration and proliferation of VSMCs. Resistin siRNA (small interfering RNA) and resistin antibody significantly inhibited migration and proliferation of VSMCs induced by conditioned medium from stretched VSMCs. Resistin protein and mRNA expression significantly increased at 14 days after carotid injury. Resistin siRNA and NAC (N-acetylcysteine) significantly reduced resistin protein and mRNA expression induced by balloon injury. Carotid artery injury increased ROS (reactive oxygen species) production. Treatment with NAC and resistin siRNA decreased ROS production. The neointimal area was significantly increased after carotid injury and was significantly reduced by resistin siRNA and NAC. In conclusion, resistin increases migration and proliferation of VSMCs, and expression of resistin in carotid artery significantly increases after injury. Resistin siRNA attenuates neointimal formation after carotid injury partly through an antioxidative mechanism. Resistin may play a pivotal role in the pathogenesis of neointimal thickening after mechanical injury.
Shyu
Kou-Gi
KG
Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Lien
Li-Ming
LM
Wang
Bao-Wei
BW
Kuan
Peiliang
P
Chang
Hang
H
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005786:Gene Expression Regulation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D052243:Resistin / Q000235:genetics / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D052243:Resistin