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Endothelial dysfunction promotes age-related reorganization of collagen fibers and alters aortic biomechanics in mice
Journal article   Peer reviewed

Endothelial dysfunction promotes age-related reorganization of collagen fibers and alters aortic biomechanics in mice

Liya Du, Jeffrey Rodgers, Nazli Gharraee, Olivia Gary, Tarek Shazly, John F Eberth and Susan M Lessner
American journal of physiology. Heart and circulatory physiology, v 328(4)
28 Mar 2025
DOI: https://doi.org/10.1152/ajpheart.00056.2023
PMID: 40062975
url
https://doi.org/10.1152/ajpheart.00056.2023View
Published, Version of Record (VoR) Open

Abstract

Passive and active vascular biomechanics Vascular remodeling Endothelial dysfunction Microstructure of extracellular matrix
Endothelial dysfunction, defined as a reduction in the bioavailability of nitric oxide (NO), is a risk factor for the occurrence and progression of various vascular diseases. This study investigates the effect of endothelial dysfunction on age-related changes in aortic extracellular matrix (ECM) microstructure and the relationship between microstructural adaptation and the mechanical response. Here, we used groups of NOS3 knockout (KO), NOS3 heterozygotes (Het), and wild type (WT) B6 mice (controls) to study changes in hemodynamic parameters, collagen fiber organization, and both active and passive aortic mechanics using biaxial pressure myography over a time course from 1.5 to 12 months. Our results show that homeostatic levels of passive circumferential stress and stretch were preserved in KO mice by remodeling adventitial collagen fibers towards a more predominantly circumferential direction with age, rather than by increased fibrosis, in response to hypertension induced by endothelial dysfunction. However, passive aortic stiffness in KO mice was significantly increased owing to geometrical changes, including significant increases in wall thickness and decreases in inner diameter, as well as by ECM microstructural reorganization, during this maladaptive vascular remodeling. Furthermore, long-term NO deficiency significantly increased smooth muscle cell (SMC) contractility initially, but this effect was attenuated with age. These findings improve our understanding of microstructural and mechanical changes during the maladaptive vascular remodeling process, demonstrating a role for adventitial collagen fiber re-orientation in the response to hypertension.

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