ArticleAging cell2019
Aging differentially modulates the Wnt pro-survival signalling pathways in vascular smooth muscle cells.
Article in Aging cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins.Cardiovascular research · 2025Article
- CCN5 Drives Leydig Cell Aging and Testicular Dysfunction: Insights into Fibrosis, Lipid Dysregulation, and Therapeutic Potential.Research (Washington, D.C.) · 2025Article
- Innovative Atherosclerosis Models: Advancing Pathophysiology and Translational Research.Research (Washington, D.C.) · 2025Review
- CCN4 (WISP-1) reduces apoptosis and atherosclerotic plaque burden in an ApoE mouse model.Atherosclerosis · 2024Article
- WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.International journal of molecular sciences · 2024Review
- Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks.International journal of molecular sciences · 2024Review
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
- Significance of the Wnt signaling pathway in coronary artery atherosclerosis.Frontiers in cardiovascular medicine · 2024Article
- MiRNA-21a, miRNA-145, and miRNA-221 Expression and Their Correlations with WNT Proteins in Patients with Obstructive and Non-Obstructive Coronary Artery Disease.International journal of molecular sciences · 2023Observational
- CCN proteins: opportunities for clinical studies-a personal perspective.Journal of cell communication and signaling · 2023Review
- The role of CCNs in controlling cellular communication in the tumor microenvironment.Journal of cell communication and signaling · 2023Review
- Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.International journal of molecular sciences · 2023Review
- Non-canonical WNT signalling in cardiovascular disease: mechanisms and therapeutic implications.Nature reviews. Cardiology · 2022Review
- How vascular smooth muscle cell phenotype switching contributes to vascular disease.Cell communication and signaling : CCS · 2022Review
- Wnt 3a Protects Myocardial Injury in Elderly Acute Myocardial Infarction by Inhibiting Serum Cystatin C/ROS-Induced Mitochondrial Damage.Frontiers in physiology · 2022Article
- Faecal miRNA profiles associated with age, sex, BMI, and lifestyle habits in healthy individuals.Scientific reports · 2021Article
- Aneurysm severity is suppressed by deletion of CCN4.Journal of cell communication and signaling · 2021Article
- LncRNA APOA1-AS facilitates proliferation and migration and represses apoptosis of VSMCs through TAF15-mediated SMAD3 mRNA stabilization.Cell cycle (Georgetown, Tex.) · 2021Article
- The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia.Ageing research reviews · 2021Review
- Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by longitudinal intravital two-photon microscopy and optical coherence tomography.American journal of physiology. Heart and circulatory physiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported pro-survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1-inducible signalling pathway protein-1 (WISP-1) consequent to β-catenin/CREB-dependent, TCF-independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP-1 was reduced. We hypothesized this disconnect could be due to aging. In this study, we elucidate the mechanism underlying Wnt3a pro-survival signalling and demonstrate the differential effect of age on Wnt3a- and Wnt5a-mediated survival. We show Wnt3a protein was expressed in human atherosclerotic coronary arteries and co-located with macrophages and VSMCs. Meanwhile, Wnt3a stimulation of primary mouse VSMCs increased β-catenin nuclear translocation and TCF, but not CREB, activation. Wnt3a increased mRNA expression of the pro-survival factor WISP-2 in a TCF-dependent manner. Functionally, β-catenin/TCF inhibition or WISP-2 neutralization significantly impaired Wnt3a-mediated VSMC survival. WISP-2 was upregulated in human atherosclerosis and partly co-localized with Wnt3a. The pro-survival action of Wnt3a was effective in VSMCs from young (2 month) and old (18-20 month) mice, whereas Wnt5a-mediated rescue was impaired with age. Further investigation revealed that although Wnt5a induced β-catenin nuclear translocation in VSMCs from both ages, CREB phosphorylation and WISP-1 upregulation did not occur in old VSMCs. Unlike Wnt5a, pro-survival Wnt3a signalling involves β-catenin/TCF and WISP-2. While Wnt3a-mediated survival was unchanged with age, Wnt5a-mediated survival was lost due to impaired CREB activation and WISP-1 regulation. Greater understanding of the effect of age on Wnt signalling may identify targets to promote VSMC survival in elderly patients with atherosclerosis.
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Registered trials
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