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Effects of Reduced Cyclic Stretch on Vascular Smooth Muscle Cell Function of Pig Carotids Perfused Ex Vivo

Gambillara, Veronica ; Thacher, Tyler ; Silacci, Paolo ; Stergiopulos, Nikos

In: American Journal of Hypertension, 2008, vol. 21, no. 4, p. 425-431

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    Titre
    • Effects of Reduced Cyclic Stretch on Vascular Smooth Muscle Cell Function of Pig Carotids Perfused Ex Vivo
    Auteur
    • Gambillara, Veronica. Laboratory of Hemodynamics and Cardiovascular Technology, Swiss Federal Institute of Technology, Lausanne, Switzerland
    • Thacher, Tyler. Laboratory of Hemodynamics and Cardiovascular Technology, Swiss Federal Institute of Technology, Lausanne, Switzerland
    • Silacci, Paolo. Laboratory of Hemodynamics and Cardiovascular Technology, Swiss Federal Institute of Technology, Lausanne, Switzerland
    • Stergiopulos, Nikos. Laboratory of Hemodynamics and Cardiovascular Technology, Swiss Federal Institute of Technology, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • American Journal of Hypertension, 2008, vol. 21, no. 4, p. 425-431. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299684
    Summary
    Background With advancing age arteries stiffen, reducing arterial compliance and leading to the development of systolic hypertension and to a substantial increase in pulse pressure. An augmented pulse pressure can be a predictor of the development of hypertension, which has been linked to several cardiovascular diseases including atherosclerosis, and to pathologies such as diabetes and renal dysfunction. In this study, we tested the hypothesis that reduced wall compliance induces pulse-pressure-mediated changes in arterial wall metabolism and remodeling. Methods Porcine carotid arteries were perfused for 24 h using an ex vivo arterial support system. Control arteries were exposed to a pulse shear stress (6 ± 3 dynes/cm2) combined with a pulse pressure of 80 ± 10 mm Hg, yielding a physiological cyclic stretch of 4-5%. A reduced compliance group was also studied, in which arteries were wrapped with an external band, thereby decreasing cyclic stretch to levels <1%. Results The experimentally reduced compliance caused a decreased contraction capacity induced by norepinephrine(NE), and this was associated with lower levels of α-smooth muscle cell-actin (α-SMC-actin) and desmin protein expressions. Arteries that were exposed to a reduced cyclic stretch exhibited a higher level of matrix metalloproteinase-2 (MMP-2) expression activity as well as an increase in Ki67 expression, thereby suggesting that matrix degradation and cellular proliferation had been initiated. Furthermore, the expression of plasminogen activator inhibitor-1 (PAI-1) in stiffened arteries was lower than in the control arteries. Conclusions These findings underline the importance of cyclic stretch in the maintenance of a differentiated and fully functional phenotype of vascular SMCs, as well as in the regulation of migratory properties, proliferation, and matrix turnover