Rationale: 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.
Conclusion: 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.
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.
Correspondence to Dr Yvonnick Bezie, Groupe Hospitalier Paris Saint-Joseph, 185 Rue Raymond Losserand, F-75674 Paris Cedex 14, France. Tel: +33 1 44 12 36 16; fax: +33 1 44 12 34 61; e-mail: firstname.lastname@example.org
Abbreviations: σ, circumferential wall stress; ECM, extracellular matrix; Einc, incremental elastic modulus; MAP, mean arterial pressure; SAD, sinoaortic denervated rats; SMC, smooth muscle cell; SNX, chemically sympathectomized rats by guanethidine
Received 25 July, 2013
Revised 8 November, 2013
Accepted 8 November, 2013