title: Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity.
abstract: Increased central vascular stiffening, assessed in vivo by determination of pulse wave velocity (PWV), is an independent predictor of cardiovascular event risk. Recent evidence demonstrates that accelerated aortic stiffening occurs in obesity; however, little is known regarding stiffening of other disease-relevant arteries or whether regional variation in arterial stiffening occurs in this setting. We addressed this gap in knowledge by assessing femoral PWV in vivo in conjunction with ex vivo analyses of femoral and coronary structure and function in a mouse model of Western diet (WD; high-fat/high-sugar)-induced obesity and insulin resistance. WD feeding resulted in increased femoral PWV in vivo. Ex vivo analysis of femoral arteries revealed a leftward shift in the strain-stress relationship, increased modulus of elasticity, and decreased compliance indicative of increased stiffness following WD feeding. Confocal and multiphoton fluorescence microscopy revealed increased femoral stiffness involving decreased elastin/collagen ratio in conjunction with increased femoral transforming growth factor-β (TGF-β) content in WD-fed mice. Further analysis of the femoral internal elastic lamina (IEL) revealed a significant reduction in the number and size of fenestrae with WD feeding. Coronary artery stiffness and structure was unchanged by WD feeding. Functionally, femoral, but not coronary, arteries exhibited endothelial dysfunction, whereas coronary arteries exhibited increased vasoconstrictor responsiveness not present in femoral arteries. Taken together, our data highlight important regional variations in the development of arterial stiffness and dysfunction associated with WD feeding. Furthermore, our results suggest TGF-β signaling and IEL fenestrae remodeling as potential contributors to femoral artery stiffening in obesity.
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri; Department of Biomedical Sciences, University of Missouri School of Medicine, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri;
authors.forename: Shawn B
authors.initials: SB
authors.lastname: Bender
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri; Department of Biological Engineering, University of Missouri, Columbia, Missouri;
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Castorena-Gonzalez
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri; Department of Medicine-Endocrinology, Diabetes and Metabolism University of Missouri School of Medicine, Columbia, Missouri.
authors.forename: Mona
authors.initials: M
authors.lastname: Garro
authors.affiliation: School of Mathematics, Computer Science and Engineering, City University London, London, United Kingdom.
authors.forename: Constantino C
authors.initials: CC
authors.lastname: Reyes-Aldasoro
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri; Department of Medicine-Endocrinology, Diabetes and Metabolism University of Missouri School of Medicine, Columbia, Missouri, Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri; and.
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
authors.affiliation: Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri; Department of Medicine-Endocrinology, Diabetes and Metabolism University of Missouri School of Medicine, Columbia, Missouri, Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri; and.
authors.forename: Vincent G
authors.initials: VG
authors.lastname: DeMarco
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri School of Medicine, Columbia, Missouri; Department of Biological Engineering, University of Missouri, Columbia, Missouri; Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri; and martinezlemusl@missouri.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Martinez-Lemus
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004549:Elastin / Q000378:metabolism; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D009928:Organ Specificity; D016212:Transforming Growth Factor beta / Q000378:metabolism; D059289:Vascular Stiffness
chemical_list: D016212:Transforming Growth Factor beta; D003094:Collagen; D004549:Elastin
keywords: confocal microscopy; coronary; femoral; pulse wave velocity