title: Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.
abstract: Hypertension and aging are both recognized to increase aortic stiffness, but their interactions are not completely understood. Most previous studies have attributed increased aortic stiffness to changes in extracellular matrix proteins that alter the mechanical properties of the vascular wall. Alternatively, we hypothesized that a significant component of increased vascular stiffness in hypertension is due to changes in the mechanical and adhesive properties of vascular smooth muscle cells, and that aging would augment the contribution from vascular smooth muscle cells when compared with the extracellular matrix. Accordingly, we studied aortic stiffness in young (16-week-old) and old (64-week-old) spontaneously hypertensive rats and Wistar-Kyoto wild-type controls. Systolic and pulse pressures were significantly increased in young spontaneously hypertensive rats when compared with young Wistar-Kyoto rats, and these continued to rise in old spontaneously hypertensive rats when compared with age-matched controls. Excised aortic ring segments exhibited significantly greater elastic moduli in both young and old spontaneously hypertensive rats versus Wistar-Kyoto rats. were isolated from the thoracic aorta, and stiffness and adhesion to fibronectin were measured by atomic force microscopy. Hypertension increased both vascular smooth muscle cell stiffness and vascular smooth muscle cell adhesion, and these increases were both augmented with aging. By contrast, hypertension did not affect histological measures of aortic collagen and elastin, which were predominantly changed by aging. These findings support the concept that stiffness and adhesive properties of vascular smooth muscle cells are novel mechanisms contributing to the increased aortic stiffness occurring with hypertension superimposed on aging.
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.).
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sehgel
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.).
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.).
authors.forename: Zhongkui
authors.initials: Z
authors.lastname: Hong
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.).
authors.forename: William C
authors.initials: WC
authors.lastname: Hunter
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.).
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.).
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.). vatnersf@njms.rutgers.edu Meiningerg@missouri.edu.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
authors.affiliation: From the Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers University, Biomedical and Health Sciences, Newark (N.L.S., W.C.H., D.E.V., S.F.V.); Department of Biomedical Engineering, New Jersey Institute of Technology, Newark (N.L.S., W.C.H.); Department of Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri, Columbia (Z.S., Z.H., M.A.H., G.A.M.). vatnersf@njms.rutgers.edu Meiningerg@missouri.edu.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Meininger
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000473:pathology; D002448:Cell Adhesion; D003094:Collagen / Q000032:analysis; D055119:Elastic Modulus; D004549:Elastin / Q000032:analysis; D022001:Focal Adhesions; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D059289:Vascular Stiffness / Q000502:physiology
chemical_list: D003094:Collagen; D004549:Elastin
keywords: aorta; collagen; elastin; fibronectins; focal adhesions; microscopy, atomic force; vascular stiffness