title: Effects of Smad decoy ODN on shear stress-induced atherosclerotic ApoE-/-mouse.
abstract: Atherosclerosis is a complex disease which involves both genetic and environmental factors in its development and progression. Shear stress is the drag force per unit area acting on the endothelium as a result of blood flow, and it plays a critical role in plaque location and progression. TGF-β1 is often regarded to have pro-atherosclerotic effect on vascular disease. TGF-β1 downstream targets Smad, for regulating a set of genes associated with atherosclerosis. Therefore, modulation of TGF-β1 and Smad expression may be the important targets for the prevention and treatment of shear stress-induced vascular disease. However, the precise mechanism of the anti-atherosclerotic effects of novel therapeutic approach has not been elucidated by using animal models regarding the shear stress-induced vascular disease. Therefore, we designed to test whether Smad decoy ODN would prevent the development of atherosclerosis in the shear stress-induced ApoE-/-mice on a western diet. We examined the effect of cast placement on the development of atherosclerosis, and the carotid artery was harvested at the sacrifice to observe histological changes. Also, we evaluated the impact of Smad decoy ODN in the regulation of genes expression related to atherosclerosis, including TGF-β1, PAI-1, and α-SMA. Our results showed that western diet with cast placement developed atherosclerosis in ApoE-/-mouse. Also, administration of Smad decoy ODN decreases the expression of TGF-β1, PAI-1, and α-SMA. These results demonstrate the potential of Smad decoy ODN to prevent the progression of atherosclerosis in ApoE-/-mouse model with western diet and shear stress.
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: An
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Woo-Ram
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Woon-Hae
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.affiliation: Department of Radiology, College of Medicine, Catholic University of Daegu Daegu, South Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Youn
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051785:Smad Proteins / Q000235:genetics* / Q000378:metabolism; D013314:Stress, Mechanical; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D009838:Oligodeoxyribonucleotides; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1
keywords: Atherosclerosis; Smad; TGF-β1; decoy; shear stress