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Enhanced p22(phox) expression impairs vascular function through p38 and ERK1/2 MAP kinase-dependent mechanisms in type 2 diabetic mice

Authors
 Modar Kassan  ;  Soo-Kyoung Choi  ;  Maria Galán  ;  Young-Ho Lee  ;  Mohamed Trebak  ;  Khalid Matrougui 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol.306(7) : 972-980, 2014 
Journal Title
 AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 
ISSN
 0363-6135 
Issue Date
2014
MeSH
Animals ; Coronary Vessels/enzymology ; Coronary Vessels/physiopathology ; Cytochrome b Group/genetics ; Cytochrome b Group/metabolism* ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/enzymology* ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/physiopathology ; Diabetic Angiopathies/enzymology* ; Diabetic Angiopathies/genetics ; Diabetic Angiopathies/physiopathology ; Diabetic Angiopathies/prevention & control ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Free Radical Scavengers/pharmacology ; Gene Expression Regulation, Enzymologic ; MAP Kinase Signaling System*/drug effects ; Male ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism* ; Mitogen-Activated Protein Kinase 3/metabolism* ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism* ; RNA Interference ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/metabolism ; Up-Regulation ; Vasodilation*/drug effects ; Vasodilator Agents/pharmacology ; p38 Mitogen-Activated Protein Kinases/metabolism*
Keywords
NADPH ; endothelium-dependent relaxation ; p22phox ; type 2 diabetes
Abstract
Type 2 diabetes is associated with vascular complication. We hypothesized that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22(phox) expression impairs vascular endothelium-dependent relaxation (EDR) in type 2 diabetes. Type 2 diabetic (db(-)/db(-)) and control (db(-)/db(+)) mice were treated with reactive oxygen species (ROS) scavenger, polyethylene glycol superoxide dismutase (1,000 U/kg daily ip), or small interfering RNA p22(phox) (p22(phox)-lentivirus-small interfering RNA, 100 μg iv, 2 times/wk) for 1 mo. EDR was impaired in microvascular bed (coronary arteriole and femoral and mesenteric resistance arteries) from diabetic mice compared with control. Interestingly, ROS scavenger and p22(phox) downregulation did not affect blood glucose level or body weight but significantly improved EDR. Mitogen-activated protein kinases (ERK1/2 and p38) phosphorylation and NADPH oxidase activity were increased in arteries from diabetic mice and were reduced after ROS scavenger or p22(phox) downregulation in db(-)/db(-) mice. The present study showed that enhanced p22(phox) expression causes vascular dysfunction through ERK1/2 and p38-mitogen-activated protein kinase-dependent mechanisms in male type 2 diabetic mice. Therefore, p22(phox) could be an important target to improve vascular function in diabetes.
Full Text
http://ajpheart.physiology.org/content/306/7/H972.long
DOI
10.1152/ajpheart.00872.2013
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Young Ho(이영호) ORCID logo https://orcid.org/0000-0002-5749-1045
Choi, Soo Kyoung(최수경) ORCID logo https://orcid.org/0000-0002-7115-6358
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99144
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