title: Increased stiffness and cell-matrix interactions of abdominal aorta in two experimental nonhypertensive models: long-term chemically sympathectomized and sinoaortic denervated rats.
abstract: BACKGROUND
  Sinoaortic denervated (SAD) and chemically sympathectomized (SNX) rats are characterized by a decrease in arterial distensibility without hypertension and would, thus, be relevant for analyzing arterial wall stiffening independently of blood pressure level. The fibronectin network, which plays a pivotal role in cell-matrix interactions, is a major determinant of arterial stiffness. We hypothesized that in SAD and SNX rats, arterial stiffness is increased, due to alterations of cell-matrix anchoring leading to spatial reorganization of the extracellular matrix.
  
  
  METHODS
  The intrinsic elastic properties of the arterial wall were evaluated in vivo by the relationship between incremental elastic modulus determined by echotracking and circumferential wall stress. The changes of cell-extracellular matrix links in the abdominal aorta were evaluated by studying fibronectin, vascular integrin receptors, and ultrastructural features of the aorta by immunochemistry.
  
  
  RESULTS
  In both experimental conditions, wall stiffness increased, associated with different modifications of cell-extracellular matrix adhesion. In SAD rats, increased media cross-sectional area was coupled with an increase of muscle cell attachments to its extracellular matrix via fibronectin and its α5-β1 integrin. In SNX rats, reduced media cross-sectional area was associated with upregulation of αv-β3 integrin and more extensive connections between dense bands and elastic fibers despite the disruption of the elastic lamellae.
  
  
  CONCLUSIONS
  In aorta of SNX and SAD rats, a similar arterial stiffness is associated to different structural alterations. An increase in αvβ3 or α5β1 integrins together with the already reported increase in the proportion of less distensible (collagen) to more distensible (elastin) components in both models contributes to remodeling and stiffening of the abdominal aorta.
authors.affiliation: aINSERM, U955, Créteil bINSERM, U1116, Nancy cDiagnosis Center and Université René Descartes, Hôtel-Dieu Hospital, UFR Médecine, Paris, France dDepartment of Anatomy and Developmental Biology, University College London, London, UK eDepartment of Pathology, Groupe Hospitalier Paris Saint-Joseph fUPMC Univ Paris 06 gCNRS UMR 7190 hDepartment of Pharmacy, Groupe Hospitalier Paris Saint-Joseph, Paris, France *P.C. and Y.B. contributed equally to the writing of the article.
authors.forename: Camille
authors.initials: C
authors.lastname: Bouissou
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
authors.forename: Hubert
authors.initials: H
authors.lastname: Dabire
authors.forename: Michel E
authors.initials: ME
authors.lastname: Safar
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gabella
authors.forename: Véronique
authors.initials: V
authors.lastname: Duchatelle
authors.forename: Pascal
authors.initials: P
authors.lastname: Challande
authors.forename: Yvonnick
authors.initials: Y
authors.lastname: Bezie
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology*; D003714:Denervation; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D006439:Hemodynamics; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D039482:Integrin alpha5 / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000294:innervation* / Q000503:physiopathology*; D013563:Sympathectomy, Chemical; D059289:Vascular Stiffness / Q000502:physiology*
chemical_list: D005353:Fibronectins; D039482:Integrin alpha5