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Aging Impairs Smooth Muscle Mediated Regulation of Aortic Stiffness: A Defect in Shock Absorption Function?
MedLine Citation:
PMID:  25128168     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Increased aortic stiffness is an early and independent biomarker of cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle cells (VSMCs) contribute significantly to aortic stiffness and investigated the mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs), and matrix to stiffness in mouse aorta preparations at optimal length and with confirmed VSMC viability were separated by the use of small molecule inhibitors and activators. Using biomechanical methods designed for minimal perturbation of cellular function, we directly quantified changes with aging in aortic material stiffness. An alpha adrenoceptor agonist, in the presence of L-NAME to remove interference of endothelial nitric oxide, increases stiffness by 90-200% from baseline in both young and old mice. Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2 in young but not old mice. Phosphotyrosine screening revealed, with aging, a biochemical signature of markedly impaired agonist-induced FA remodeling previously associated with Src signaling. Protein expression measurement confirmed a decrease in Src expression with aging. Thus, we report here an additive model for the in vitro biomechanical components of the mouse aortic wall in which: 1) VSMCs are a surprisingly large component of aortic stiffness at physiologic lengths and 2) regulation of the VSMC component through FA signaling and hence plasticity is impaired with aging, diminishing the aorta's normal shock absorption function in response to stressors.
Authors:
Yuan Z Gao; Robert J Saphirstein; Rina Yamin; Béla Suki; Kathleen G Morgan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-15
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
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