title: Glycated collagen alters endothelial cell actin alignment and nitric oxide release in response to fluid shear stress.
abstract: People with diabetes suffer from early accelerated atherosclerosis, which contributes to morbidity and mortality from myocardial infarction, stroke, and peripheral vascular disease. Atherosclerosis is thought to initiate at sites of endothelial cell injury. Hyperglycemia, a hallmark of diabetes, leads to non-enzymatic glycosylation (or glycation) of extracellular matrix proteins. Glycated collagen alters endothelial cell function and could be an important factor in atherosclerotic plaque development. This study examined the effect of collagen glycation on endothelial cell response to fluid shear stress. Porcine aortic endothelial cells were grown on native or glycated collagen and exposed to shear stress using an in vitro parallel plate system. Cells on native collagen elongated and aligned in the flow direction after 24 h of 20 dynes/cm(2) shear stress, as indicated by a 13% decrease in actin fiber angle distribution standard deviation. However, cells on glycated collagen did not align. Shear stress-mediated nitric oxide release by cells on glycated collagen was half that of cells on native collagen, which correlated with decreased endothelial nitric oxide synthase (eNOS) phosphorylation. Glycated collagen likely inhibited cell shear stress response through altered cell-matrix interactions, since glycated collagen attenuated focal adhesion kinase activation with shear stress. When focal adhesion kinase was pharmacologically blocked in cells on native collagen, eNOS phosphorylation with flow was reduced in a manner similar to that of glycated collagen. These detrimental effects of glycated collagen on endothelial cell response to shear stress may be an important contributor to accelerated atherosclerosis in people with diabetes.
authors.affiliation: Drexel University, Department of Mechanical Engineering and Mechanics, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Kemeny
authors.forename: Dannielle S
authors.initials: DS
authors.lastname: Figueroa
authors.forename: Allison M
authors.initials: AM
authors.lastname: Andrews
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Barbee
authors.forename: Alisa Morss
authors.initials: AM
authors.lastname: Clyne
mesh_terms: D000199:Actins / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000166:cytology; D050197:Atherosclerosis / Q000473:pathology; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D003920:Diabetes Mellitus / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D009569:Nitric Oxide / Q000737:chemistry*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D033081:Shear Strength; D013314:Stress, Mechanical; D013552:Swine
chemical_list: D000199:Actins; D009569:Nitric Oxide; D003094:Collagen; D052250:Nitric Oxide Synthase Type III; D051416:Focal Adhesion Protein-Tyrosine Kinases