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Diet alters age-related remodeling of aortic collagen in mice susceptible to atherosclerosis
Journal article   Open access   Peer reviewed

Diet alters age-related remodeling of aortic collagen in mice susceptible to atherosclerosis

Shana R Watson, Kara M Cooper, Piaomu Liu, Nazli Gharraee, Liya Du, Savannah M Han, Edsel A Peña, Michael A Sutton, John F Eberth and Susan M Lessner
American journal of physiology. Heart and circulatory physiology, v 320(1), pp H52-H65
01 Jan 2021
DOI: https://doi.org/10.1152/ajpheart.00420.2020
PMID: 33373275
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847077View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Age Factors Animals Aorta, Abdominal - metabolism Aorta, Abdominal - pathology Aorta, Abdominal - physiopathology Aorta, Thoracic - metabolism Aorta, Thoracic - pathology Aorta, Thoracic - physiopathology Aortic Diseases - genetics Aortic Diseases - metabolism Aortic Diseases - pathology Aortic Diseases - physiopathology Atherosclerosis - genetics Atherosclerosis - metabolism Atherosclerosis - pathology Atherosclerosis - physiopathology Diet, Western Disease Models, Animal Female Fibrillar Collagens - metabolism Male Mice Mice, Knockout, ApoE Vascular Remodeling Vasoconstriction
Vascular cells restructure extracellular matrix in response to aging or changes in mechanical loading. Here, we characterized collagen architecture during age-related aortic remodeling in atherosclerosis-prone mice. We hypothesized that changes in collagen fiber orientation reflect an altered balance between passive and active forces acting on the arterial wall. We examined two factors that can alter this balance, endothelial dysfunction and reduced smooth muscle cell (SMC) contractility. Collagen fiber organization was visualized by second-harmonic generation microscopy in aortic adventitia of apolipoprotein E (apoE) knockout (KO) mice at 6 wk and 6 mo of age on a chow diet and at 7.5 mo of age on a Western diet (WD), using image analysis to yield mean fiber orientation. Adventitial collagen fibers became significantly more longitudinally oriented with aging in apoE knockout mice on chow diet. Conversely, fibers became more circumferentially oriented with aging in mice on WD. Total collagen content increased significantly with age in mice fed WD. We compared expression of endothelial nitric oxide synthase and acetylcholine-mediated nitric oxide release but found no evidence of endothelial dysfunction in older mice. Time-averaged volumetric blood flow in all groups showed no significant changes. Wire myography of aortic rings revealed decreases in active stress generation with age that were significantly exacerbated in WD mice. We conclude that the aorta displays a distinct remodeling response to atherogenic stimuli, indicated by altered collagen organization. Collagen reorganization can occur in the absence of altered hemodynamics and may represent an adaptive response to reduced active stress generation by vascular SMCs. The following major observations were made in this study: ) aortic adventitial collagen fibers become more longitudinally oriented with aging in apolipoprotein E knockout mice fed a chow diet; ) conversely, adventitial collagen fibers become more circumferentially oriented with aging in apoE knockout mice fed a high-fat diet; ) adventitial collagen content increases significantly with age in mice on a high-fat diet; ) these alterations in collagen organization occur largely in the absence of hemodynamic changes; and ) circumferential reorientation of collagen is associated with decreased active force generation (contractility) in aged mice on a high-fat diet.

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11 citations in Web of Science
9 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Cardiac & Cardiovascular Systems
Peripheral Vascular Disease
Physiology
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