Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases

Arterial stiffening is a significant risk factor for the development of cardiovascular diseases, including hypertension, atherosclerosis, and arteriopathy. The destruction of elastic fibers, accompanied by vascular inflammatory remodeling, is a key process in the progression of arterial stiffening a...

Full description

Saved in:
Bibliographic Details
Main Authors: Mingyi Wang, Kimberly R. McGraw, Robert E. Monticone, Gianfranco Pintus
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/15/2/153
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849718542650310656
author Mingyi Wang
Kimberly R. McGraw
Robert E. Monticone
Gianfranco Pintus
author_facet Mingyi Wang
Kimberly R. McGraw
Robert E. Monticone
Gianfranco Pintus
author_sort Mingyi Wang
collection DOAJ
description Arterial stiffening is a significant risk factor for the development of cardiovascular diseases, including hypertension, atherosclerosis, and arteriopathy. The destruction of elastic fibers, accompanied by vascular inflammatory remodeling, is a key process in the progression of arterial stiffening and related pathologies. In young, healthy arteries, intact elastic fibers create a resilient microenvironment that maintains the quiescence of arterial cells. However, with advancing age, these elastic fibers undergo post-translational modifications, such as oxidation, glycosylation, and calcification, leading to their eventual degeneration. This degeneration results in the release of degraded peptides and the formation of an inflammatory, stiffened niche. Elastic fiber degeneration profoundly impacts the proinflammatory phenotypes and behaviors of various arterial cells, including endothelial cells, smooth muscle cells, macrophages, fibroblasts, and mast cells. Notably, the degraded elastic fibers release elastin-derived peptides (EDPs), which act as potent inflammatory molecules. EDPs activate various arterial cellular processes, including inflammatory secretion, cell migration, proliferation, and calcification, by interacting with the elastin receptor complex (ERC). These elastin-related cellular events are commonly observed with aging and in diseased arteries. These findings suggest that the degeneration of the elastic fiber meshwork is a primary event driving arterial inflammation, stiffening, and adverse remodeling with advancing age. Therefore, preserving elastic fibers and blocking the EDP/ERC signaling pathways may offer promising therapeutic strategies for mitigating age-related arterial remodeling and related arterial diseases.
format Article
id doaj-art-62eea8af281e44bc9314d70ae5f0843f
institution DOAJ
issn 2218-273X
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Biomolecules
spelling doaj-art-62eea8af281e44bc9314d70ae5f0843f2025-08-20T03:12:20ZengMDPI AGBiomolecules2218-273X2025-01-0115215310.3390/biom15020153Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial DiseasesMingyi Wang0Kimberly R. McGraw1Robert E. Monticone2Gianfranco Pintus3Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USALaboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USALaboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USADepartment of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, ItalyArterial stiffening is a significant risk factor for the development of cardiovascular diseases, including hypertension, atherosclerosis, and arteriopathy. The destruction of elastic fibers, accompanied by vascular inflammatory remodeling, is a key process in the progression of arterial stiffening and related pathologies. In young, healthy arteries, intact elastic fibers create a resilient microenvironment that maintains the quiescence of arterial cells. However, with advancing age, these elastic fibers undergo post-translational modifications, such as oxidation, glycosylation, and calcification, leading to their eventual degeneration. This degeneration results in the release of degraded peptides and the formation of an inflammatory, stiffened niche. Elastic fiber degeneration profoundly impacts the proinflammatory phenotypes and behaviors of various arterial cells, including endothelial cells, smooth muscle cells, macrophages, fibroblasts, and mast cells. Notably, the degraded elastic fibers release elastin-derived peptides (EDPs), which act as potent inflammatory molecules. EDPs activate various arterial cellular processes, including inflammatory secretion, cell migration, proliferation, and calcification, by interacting with the elastin receptor complex (ERC). These elastin-related cellular events are commonly observed with aging and in diseased arteries. These findings suggest that the degeneration of the elastic fiber meshwork is a primary event driving arterial inflammation, stiffening, and adverse remodeling with advancing age. Therefore, preserving elastic fibers and blocking the EDP/ERC signaling pathways may offer promising therapeutic strategies for mitigating age-related arterial remodeling and related arterial diseases.https://www.mdpi.com/2218-273X/15/2/153ageelastic fiberselastic laminaearterial cellsarterial remodelingarterial stiffness
spellingShingle Mingyi Wang
Kimberly R. McGraw
Robert E. Monticone
Gianfranco Pintus
Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
Biomolecules
age
elastic fibers
elastic laminae
arterial cells
arterial remodeling
arterial stiffness
title Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
title_full Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
title_fullStr Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
title_full_unstemmed Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
title_short Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
title_sort unraveling elastic fiber derived signaling in arterial aging and related arterial diseases
topic age
elastic fibers
elastic laminae
arterial cells
arterial remodeling
arterial stiffness
url https://www.mdpi.com/2218-273X/15/2/153
work_keys_str_mv AT mingyiwang unravelingelasticfiberderivedsignalinginarterialagingandrelatedarterialdiseases
AT kimberlyrmcgraw unravelingelasticfiberderivedsignalinginarterialagingandrelatedarterialdiseases
AT robertemonticone unravelingelasticfiberderivedsignalinginarterialagingandrelatedarterialdiseases
AT gianfrancopintus unravelingelasticfiberderivedsignalinginarterialagingandrelatedarterialdiseases