| Title: |
Endothelial Dysfunction Promotes Age-Related Reorganization of Collagen Fibers and Alters Aortic Biomechanics in Mice |
| Authors: |
Du, Liya; Rodgers, Jeffrey; Gharraee, Nazli; Gary, Olivia; Shazly, Tarek; Eberth, John F.; Lessner, Susan M |
| Source: |
Faculty Publications |
| Publisher Information: |
Scholar Commons |
| Publication Year: |
2025 |
| Collection: |
University of South Carolina Libraries: Scholar Commons |
| Subject Terms: |
endothelial dysfunction; microstructure of extracellular matrix; passive and active vascular biomechanics; vascular remodeling; Biomedical Engineering and Bioengineering; Engineering |
| Description: |
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 mo. Our results show that homeostatic levels of passive circumferential stress and stretch were preserved in KO mice by remodeling adventitial collagen fibers toward 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, and 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 reorientation in the response to hypertension. |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://scholarcommons.sc.edu/bmen_facpub/19; https://scholarcommons.sc.edu/context/bmen_facpub/article/1020/viewcontent/du_et_al_2025_endothelial_dysfunction_promotes_age_related_reorganization_of_collagen_fibers_and_alters_aortic.pdf |
| DOI: |
10.1152/ajpheart.00056.2023; |
| Availability: |
https://scholarcommons.sc.edu/bmen_facpub/19; https://doi.org/10.1152/ajpheart.00056.2023;; https://scholarcommons.sc.edu/context/bmen_facpub/article/1020/viewcontent/du_et_al_2025_endothelial_dysfunction_promotes_age_related_reorganization_of_collagen_fibers_and_alters_aortic.pdf |
| Rights: |
© 2025 The Authors. Licensed under Creative Commons Attribution CC-BY-NC-ND 4.0 . Published by the American Physiological Society. |
| Accession Number: |
edsbas.756B5ABC |
| Database: |
BASE |