ArticleThe Journal of biological chemistry2013
Noncanonical matrix metalloprotease-1-protease-activated receptor-1 signaling triggers vascular smooth muscle cell dedifferentiation and arterial stenosis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- Aerobic Exercise Ameliorates Adverse Vascular Remodeling in Diabetes via PDK1/FoxO1 Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Protease-activated receptors in vascular smooth muscle cells: a bridge between thrombo-inflammation and vascular remodelling.Cell communication and signaling : CCS · 2025Review
- Suppression of Heart Failure With PAR1 Pepducin Technology in a Pressure Overload Model in Mice.Circulation. Heart failure · 2023Article
- Blockade of CD47 function attenuates restenosis by promoting smooth muscle cell efferocytosis and inhibiting their migration and proliferation.The Journal of biological chemistry · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- AK098656: a new biomarker of coronary stenosis severity in hypertensive and coronary heart disease patients.Diabetology & metabolic syndrome · 2022Article
- PINK1-Dependent Mitophagy Reduced Endothelial Hyperpermeability and Cell Migration Capacity Under Simulated Microgravity.Frontiers in cell and developmental biology · 2022Article
- Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish.iScience · 2021Article
- Deficiency of MMP1a (Matrix Metalloprotease 1a) Collagenase Suppresses Development of Atherosclerosis in Mice: Translational Implications for Human Coronary Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- FAM19A (TAFA): An Emerging Family of Neurokines with Diverse Functions in the Central and Peripheral Nervous System.ACS chemical neuroscience · 2021Review
- Up-regulation of FoxO1 contributes to adverse vascular remodelling in type 1 diabetic rats.Journal of cellular and molecular medicine · 2020Article
- Inhibition of lysine-specific demethylase 1A suppresses neointimal hyperplasia by targeting bone morphogenetic protein 2 and mediating vascular smooth muscle cell phenotype.Cell proliferation · 2020Article
- Atherosclerosis and the Capillary Network; Pathophysiology and Potential Therapeutic Strategies.Cells · 2019Review
- Protease Activity in Vascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- MicroRNA hsa-miR-623 directly suppresses MMP1 and attenuates IL-8-induced metastasis in pancreatic cancer.International journal of oncology · 2019Article
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach.International journal of molecular sciences · 2018Review
- Protease-activated receptor 1 inhibits cholesterol efflux and promotes atherogenesis via cullin 3-mediated degradation of the ABCA1 transporter.The Journal of biological chemistry · 2018Article
- Noncanonical Matrix Metalloprotease 1-Protease-Activated Receptor 1 Signaling Drives Progression of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- LIM and cysteine-rich domains 1 is required for thrombin-induced smooth muscle cell proliferation and promotes atherogenesis.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular injury that results in proliferation and dedifferentiation of vascular smooth muscle cells (SMCs) is an important contributor to restenosis following percutaneous coronary interventions or plaque rupture. Protease-activated receptor-1 (PAR1) has been shown to play a role in vascular repair processes; however, little is known regarding its function or the relative roles of the upstream proteases thrombin and matrix metalloprotease-1 (MMP-1) in triggering PAR1-mediated arterial restenosis. The goal of this study was to determine whether noncanonical MMP-1 signaling through PAR1 would contribute to aberrant vascular repair processes in models of arterial injury. A mouse carotid arterial wire injury model was used for studies of neointima hyperplasia and arterial stenosis. The mice were treated post-injury for 21 days with a small molecule inhibitor of MMP-1 or a direct thrombin inhibitor and compared with vehicle control. Intimal and medial hyperplasia was significantly inhibited by 2.8-fold after daily treatment with the small molecule MMP-1 inhibitor, an effect that was lost in PAR1-deficient mice. Conversely, chronic inhibition of thrombin showed no benefit in suppressing the development of arterial stenosis. Thrombin-PAR1 signaling resulted in a supercontractile, differentiated phenotype in SMCs. Noncanonical MMP-1-PAR1 signaling resulted in the opposite effect and led to a dedifferentiated phenotype via a different G protein pathway. MMP-1-PAR1 significantly stimulated hyperplasia and migration of SMCs, and resulted in down-regulation of SMC contractile genes. These studies provide a new mechanism for the development of vascular intimal hyperplasia and suggest a novel therapeutic strategy to suppress restenosis by targeting noncanonical MMP-1-PAR1 signaling in vascular SMCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.