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Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy

 Se-Jung Yoon  ;  Young Won Yoon  ;  Byoung Kwon Lee  ;  Hyuck Moon Kwon  ;  Ki-Chul Hwang  ;  Myunghyun Kim  ;  Woochul Chang  ;  Bum-Kee Hong  ;  Young-Ho Lee  ;  Soon-Jung Park  ;  Pil-Ki Min  ;  Se-Joong Rim 
Journal Title
Issue Date
Animals ; Aorta/metabolism ; Aorta/pathology ; Cell Proliferation/drug effects ; Cyclooxygenase 2/metabolism ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Diabetic Angiopathies/drug therapy* ; Diabetic Angiopathies/metabolism* ; Diabetic Angiopathies/pathology ; Glycation End Products, Advanced/metabolism* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Male ; Myocytes, Smooth Muscle/metabolism* ; Myocytes, Smooth Muscle/pathology ; Oxidative Stress/drug effects* ; Proto-Oncogene Proteins c-jun/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Simvastatin/pharmacology* ; Simvastatin/therapeutic use ; Transcription Factor RelA/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
cyclooxygenase 2 ; diabetes mellitus ; extracellular signal-regulated MAP kinases ; hydroxymethylglutaryl-CoA reductase inhibitors ; muscle ; smooth ; vascular ; NFκB ; p38 mitogen-activated protein kinases ; proto-oncogene proteins c-jun ; reactive oxygen species
Advanced glycation endproducts (AGEs)-induced vascular smooth muscle cell (VSMCs) proliferation and formation of reactive oxygen species (ROS) are emerging as one of the important mechanisms of diabetic vasculopathy but little is known about the antioxidative action of HMG CoA reductase inhibitor (statin) on AGEs. We hypothesized that statin might reduce AGEs-induced intracellular ROS of VSMCs and analyzed the possible mechanism of action of statin in AGEs-induced cellular signaling. Aortic smooth muscle cell of Sprague-Dawley rat (RASMC) culture was done using the different levels of AGEs stimulation in the presence or absence of statin. The proliferation of RASMC, ROS formation and cellular signaling was evaluated and neointimal formation after balloon injury in diabetic rats was analyzed. Increasing concentration of AGEs stimulation was associated with increased RASMC proliferation and increased ROS formation and they were decreased with statin in a dose-dependent manner. Increased NF-kappaB p65, phosphorylated ERK, phosphorylated p38 MAPK, cyclooxygenase-2, and c-jun by AGEs stimulation were noted and their expression was inhibited by statin. Neointimal formation after balloon injury was much thicker in diabetic rats than the sham-treated group but less neointimal growth was observed in those treated with statin after balloon injury. Increased ROS formation, subsequent activation of MAPK system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kwon, Hyuck Moon(권혁문) ORCID logo https://orcid.org/0000-0001-9901-5015
Min, Pil Ki(민필기) ORCID logo https://orcid.org/0000-0001-7033-7651
Park, Soon Jung(박순정) ORCID logo https://orcid.org/0000-0002-0423-1944
Yoon, Young Won(윤영원) ORCID logo https://orcid.org/0000-0002-0907-0350
Lee, Byoung Kwon(이병권) ORCID logo https://orcid.org/0000-0001-9259-2776
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
Rim, Se Joong(임세중) ORCID logo https://orcid.org/0000-0002-7631-5581
Chang, Woo Chul(장우철)
Hong, Bum Kee(홍범기) ORCID logo https://orcid.org/0000-0002-6456-0184
Hwang, Ki Chul(황기철)
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