title: Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice.
abstract: The aim of this study was to characterize alterations in vascular structure and mechanics in murine mesenteric arteries from obese non-hypertensive mice, as well as their relationship with adipokines. Four-week old C57BL/6J male mice were assigned either to a control (C, 10% kcal from fat) or a high-fat diet (HFD, 45% kcal from fat) for 32weeks. HFD animals weighed 30% more than controls (p<0.001), exhibited similar blood pressure, increased leptin, insulin and superoxide anion (O2(-)) levels, and reduced adiponectin levels and nitric oxide (NO) bioavailability. Arterial structure showed an outward remodeling with an increase in total number of both adventitial and smooth muscle cells in HFD. Moreover, HFD mice exhibited an increased arterial stiffness assessed by β-values (C=2.4±0.5 vs HFD=5.3±0.8; p<0.05) and aortic pulse wave velocity (PWV, C=3.4±0.1 vs HFD=3.9±0.1; p<0.05). β-Values and PWV positively correlated with leptin, insulin or O2(-) levels, whereas they negatively correlated with adiponectin levels and NO bioavailability (p<0.01). A reduction in fenestrae number together with an increase in type-I collagen amount (p<0.05) were observed in HFD. These data demonstrate that HFD accounts for the development of vascular remodeling and arterial stiffness associated with adipokine dysregulation and oxidative stress, independently of hypertension development.
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gil-Ortega
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Martín-Ramos
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Arribas
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: González
authors.affiliation: Departamento de Bioquímica, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Aránguez
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Ruiz-Gayo
authors.affiliation: Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain. Electronic address: bsomoza.fcex@ceu.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Somoza
authors.affiliation: Instituto Pluridisciplinar and Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
authors.forename: María S
authors.initials: MS
authors.lastname: Fernández-Alfonso
mesh_terms: D054392:Adipokines / Q000097:blood* / Q000276:immunology; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000276:immunology; D008297:Male; D008638:Mesenteric Arteries / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009765:Obesity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000276:immunology; D063177:Pulse Wave Analysis; D066253:Vascular Remodeling / Q000502:physiology; D059289:Vascular Stiffness / Q000276:immunology / Q000502:physiology*
chemical_list: D054392:Adipokines
keywords: Adipokine; Arterial remodeling; Arterial stiffness; Diet-induced obesity; Oxidative stress