ArticleJournal of cellular and molecular medicine2017
MicroRNA-203 mimics age-related aortic smooth muscle dysfunction of cytoskeletal pathways.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- DNA Methylation-Guided Prediction and Validation of TAAD Molecular Targets.Biochemical genetics · 2026Article
- Dystrophin and dystrophin association protein expression decreases with age in vascular smooth muscle.GeroScience · 2026Article
- Regulation of transglutaminase-2 and related miRNAs expression by calorie restriction in aorta of aging female mice.Molecular biology reports · 2025Article
- Pharmacological activation of NO-sensitive guanylyl cyclase ameliorates obesity-induced arterial stiffness.Vascular pharmacology · 2025Article
- miR-632 Induces DNAJB6 Inhibition Stimulating Endothelial-to-Mesenchymal Transition and Fibrosis in Marfan Syndrome Aortopathy.International journal of molecular sciences · 2023Article
- Progressive aortic stiffness in aging C57Bl/6 mice displays altered contractile behaviour and extracellular matrix changes.Communications biology · 2022Article
- Ageing causes an aortic contractile dysfunction phenotype by targeting the expression of members of the extracellular signal-regulated kinase pathway.Journal of cellular and molecular medicine · 2022Article
- Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.Arteriosclerosis, thrombosis, and vascular biology · 2022Observational
- Extracellular Matrix in Aging Aorta.Frontiers in cell and developmental biology · 2022Review
- Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix.International journal of molecular sciences · 2021Review
- Aging-induced microbleeds of the mouse thalamus compared to sensorimotor and memory defects.Neurobiology of aging · 2021Article
- BCL11B Regulates Arterial Stiffness and Related Target Organ Damage.Circulation research · 2021Article
- Non-muscle myosin II regulates aortic stiffness through effects on specific focal adhesion proteins and the non-muscle cortical cytoskeleton.Journal of cellular and molecular medicine · 2021Article
- Vascular aging, the vascular cytoskeleton and aortic stiffness.Exploration of medicine · 2021Article
- Deciphering the Role of microRNAs in Large-Artery Stiffness Associated With Aging: Focus on miR-181b.Frontiers in physiology · 2021Review
- Noncoding RNAs in Vascular Aging.Oxidative medicine and cellular longevity · 2020Review
- Involvement of Epigenetic Mechanisms and Non-coding RNAs in Blood-Brain Barrier and Neurovascular Unit Injury and Recovery After Stroke.Frontiers in neuroscience · 2019Review
- Non-genomic Effects of Estrogen on Cell Homeostasis and Remodeling With Special Focus on Cardiac Ischemia/Reperfusion Injury.Frontiers in endocrinology · 2019Review
- Reversal of Aging-Induced Increases in Aortic Stiffness by Targeting Cytoskeletal Protein-Protein Interfaces.Journal of the American Heart Association · 2018Article
- Role of miRNA in the Regulatory Mechanisms of Estrogens in Cardiovascular Ageing.Oxidative medicine and cellular longevity · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased aortic stiffness is a biomarker for subsequent adverse cardiovascular events. We have previously reported that vascular smooth muscle Src-dependent cytoskeletal remodelling, which contributes to aortic plasticity, is impaired with ageing. Here, we use a multi-scale approach to determine the molecular mechanisms behind defective Src-dependent signalling in an aged C57BL/6 male mouse model. Increased aortic stiffness, as measured in vivo by pulse wave velocity, was found to have a comparable time course to that in humans. Bioinformatic analyses predicted several miRs to regulate Src-dependent cytoskeletal remodelling. qRT-PCR was used to determine the relative levels of predicted miRs in aortas and, notably, the expression of miR-203 increased almost twofold in aged aorta. Increased miR-203 expression was associated with a decrease in both mRNA and protein expression of Src, caveolin-1 and paxillin in aged aorta. Probing with phospho-specific antibodies confirmed that overexpression of miR-203 significantly attenuated Src and extracellular signal regulated kinase (ERK) signalling, which we have previously found to regulate vascular smooth muscle stiffness. In addition, transfection of miR-203 into aortic tissue from young mice increased phenylephrine-induced aortic stiffness ex vivo, mimicking the aged phenotype. Upstream of miR-203, we found that DNA methyltransferases (DNMT) 1, 3a, and 3b are also significantly decreased in the aged mouse aorta and that DNMT inhibition significantly increases miR-203 expression. Thus, the age-induced increase in miR-203 may be caused by epigenetic promoter hypomethylation in the aorta. These findings indicate that miR-203 promotes a re-programming of Src/ERK signalling pathways in vascular smooth muscle, impairing the regulation of stiffness in aged aorta.
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