ArticleCardiovascular research2025
Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins.
Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Enzymatic and non-enzymatic oxidation of fibrillar collagen.Redox report : communications in free radical research · 2026Review
- Hyaluronan deficiency disrupts endothelial glycocalyx integrity and contributes to age-related arterial dysfunction.GeroScience · 2026Article
- Serum Mucin-1 (CA15-3) in Relation to Pulse Pressure Amplification in Untreated Chinese Patients.Journal of clinical hypertension (Greenwich, Conn.) · 2026Article
- Facilitated DNA damage repair as an emerging therapeutic strategy for inflammatory and fibrotic diseases.RSC chemical biology · 2026Review
- Mitochondrial dysfunction in endothelial senescence: implications for vascular remodeling and therapeutic strategies.Archives of pharmacal research · 2026Review
- Oxidative Stress-Induced DNA Damage Response Pathways in Aortic Disease: Implications for Inflammation and Vascular Degeneration.International journal of molecular sciences · 2026Review
- Nucleobase catalysts for the enzymatic activation of 8-oxoguanine DNA glycosylase 1.RSC chemical biology · 2026Article
- Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Anti-senescence therapies: a new concept to address cardiovascular disease.Cardiovascular research · 2025Review
- Utilization of natural products in diverse pathogeneses of diseases associated with single or double DNA strand damage repair.Chinese medicine · 2025Review
- Acetyltransferase in cardiovascular disease and aging.The journal of cardiovascular aging · 2024Article
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Authors and funding
14 authors.
Funding
Abstract
aimsVascular ageing is characterized by vessel stiffening, with increased deposition of extracellular matrix (ECM) proteins including collagens. Oxidative DNA damage occurs in vascular ageing, but how it regulates ECM proteins and vascular stiffening is unknown. We sought to determine the relationship between oxidative DNA damage and ECM regulatory proteins in vascular ageing. METHODS AND
resultsWe examined oxidative DNA damage, the major base excision repair (BER) enzyme 8-Oxoguanine DNA Glycosylase (Ogg1) and its regulators, multiple physiological markers of ageing, and ECM proteomics in mice from 22 to 72 w. Vascular ageing was associated with increased oxidative DNA damage, and decreased expression of Ogg1, its active acetylated form, its acetylation regulatory proteins P300 and CBP, and the transcription factor Foxo3a. Vascular stiffness was examined in vivo in control, Ogg1-/-, or mice with vascular smooth muscle cell-specific expression of Ogg1+ (Ogg1) or an inactive mutation (Ogg1KR). Ogg1-/- and Ogg1KR mice showed reduced arterial compliance and distensibility, and increased stiffness and pulse pressure, whereas Ogg1 expression normalized all parameters to 72 w. ECM proteomics identified major changes in collagens with ageing, and downregulation of the ECM regulatory proteins Protein 6-lysyl oxidase (LOX) and WNT1-inducible-signaling pathway protein 2 (WISP2). Ogg1 overexpression upregulated LOX and WISP2 both in vitro and in vivo, and downregulated Transforming growth factor β1 (TGFb1) and Collagen 4α1 in vivo compared with Ogg1KR. Foxo3a activation induced Lox, while Wnt3 induction of Wisp2 also upregulated LOX and Foxo3a, and downregulated TGFβ1 and fibronectin 1. In humans, 8-oxo-G increased with vascular stiffness, while active OGG1 reduced with both age and stiffness.
conclusionVascular ageing is associated with oxidative DNA damage, downregulation of major BER proteins, and changes in multiple ECM structural and regulatory proteins. Ogg1 protects against vascular ageing, associated with changes in ECM regulatory proteins including LOX and WISP2.
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