ArticleScientific reports2015
Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Plasma Protein Profile of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure in 2 Cohorts.Journal of the American Heart Association · 2021Pooled it
- Identification of distinct and shared biomarker panels in different manifestations of cerebral small-vessel disease through proteomic profiling.Nature aging · 2026Article
- Evaluating the Causal Roles of Matrix Metalloproteinases in Metabolic Syndrome: A Mendelian Randomization Study Highlighting MMP12 in Blood Pressure Regulation.Genetics research · 2026Article
- Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.medRxiv : the preprint server for health sciences · 2025Article
- Causal relationship between serum metalloproteinase 12 levels and aortic dissection and aortic aneurysm: a bidirectional Mendelian randomization study.Journal of thoracic disease · 2025Article
- Transcriptomic and Multi-scale Network Analyses Reveal Key Drivers of Cardiovascular Disease.IEEE transactions on molecular, biological, and multi-scale communications · 2025Article
- Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.International journal of molecular sciences · 2024Article
- Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging.Aging cell · 2024Article
- Loss-of-function G6PD variant moderated high-fat diet-induced obesity, adipocyte hypertrophy, and fatty liver in male rats.The Journal of biological chemistry · 2024Article
- Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy.American journal of respiratory and critical care medicine · 2024Article
- Arterial Mechanics, Extracellular Matrix, and Smooth Muscle Differentiation in Carotid Arteries Deficient for Rac1.Annals of vascular medicine and research · 2024Article
- Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.International journal of molecular sciences · 2023Article
- Survivin as a mediator of stiffness-induced cell cycle progression and proliferation of vascular smooth muscle cells.APL bioengineering · 2023Article
- Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease.Nature communications · 2023Article
- CXCR6 Mediates Pressure Overload-Induced Aortic Stiffness by Increasing Macrophage Recruitment and Reducing Exosome-miRNA29b.Journal of cardiovascular translational research · 2023Article
- Engineering Smooth Muscle to Understand Extracellular Matrix Remodeling and Vascular Disease.Bioengineering (Basel, Switzerland) · 2022Review
- Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice.Journal of biomechanics · 2022Article
- Mechanosensitive smooth muscle cell phenotypic plasticity emerging from a null state and the balance between Rac and Rho.Cell reports · 2021Article
- PPARγ activation improves the microenvironment of perivascular adipose tissue and attenuates aortic stiffening in obesity.Journal of biomedical science · 2021Article
- Blackcurrant (Nutrients · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Arterial stiffening is a hallmark of aging and risk factor for cardiovascular disease, yet its regulation is poorly understood. Here we use mouse modeling to show that matrix metalloproteinase-12 (MMP12), a potent elastase, is essential for acute and chronic arterial stiffening. MMP12 was induced in arterial smooth muscle cells (SMCs) after acute vascular injury. As determined by genome-wide analysis, the magnitude of its gene induction exceeded that of all other MMPs as well as those of the fibrillar collagens and lysyl oxidases, other common regulators of tissue stiffness. A preferential induction of SMC MMP12, without comparable effect on collagen abundance or structure, was also seen during chronic arterial stiffening with age. In both settings, deletion of MMP12 reduced elastin degradation and blocked arterial stiffening as assessed by atomic force microscopy and immunostaining for stiffness-regulated molecular markers. Isolated MMP12-null SMCs sense extracellular stiffness normally, indicating that MMP12 causes arterial stiffening by remodeling the SMC microenvironment rather than affecting the mechanoresponsiveness of the cells themselves. In human aortic samples, MMP12 levels strongly correlate with markers of SMC stiffness. We conclude that MMP12 causes arterial stiffening in mice and suggest that it functions similarly in humans.
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