ArticleEuropean heart journal2022
Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis.
Article in European heart journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026Review
- Molecular basis of coronary artery disease-malignancy comorbidity: inflammation, immunometabolism, thrombosis, and cardio-oncology translation.Frontiers in immunology · 2026Review
- Recent advances in the design and development of small-molecule MMP-2 inhibitors.Future medicinal chemistry · 2025Review
- Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks.International journal of molecular sciences · 2025Review
- The Hidden Price of Plenty: Oxidative Stress and Calorie-Induced Cardiometabolic Dysfunction.Life (Basel, Switzerland) · 2025Review
- Hair Calcium Levels in Relation to Coronary Artery Disease Severity and Systemic Inflammation Markers: A Pilot Study.Journal of clinical medicine · 2025Article
- Wogonin Attenuates Atherosclerosis via KLF11-Mediated Suppression of PPARα-YAP1-Driven Glycolysis and Enhancement of ABCA1/G1-Mediated Cholesterol Efflux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- An enzymatic cleavage-triggered minimally invasive nanosensor for urine-based detection of early atherosclerosis.Science advances · 2025Article
- The Peripheral Amyloid-β Nexus: Connecting Alzheimer's Disease with Atherosclerosis through Shared Pathophysiological Mechanisms.Neuromolecular medicine · 2025Review
- Review
- The Complex Role of Matrix Metalloproteinase-2 (MMP-2) in Health and Disease.International journal of molecular sciences · 2024Review
- Neutrophil extracellular traps: a catalyst for atherosclerosis.Molecular and cellular biochemistry · 2024Review
- Single chain fragment variable, a new theranostic approach for cardiovascular diseases.Frontiers in immunology · 2024Review
- Platelets as crucial players in the dynamic interplay of inflammation, immunity, and cancer: unveiling new strategies for cancer prevention.Frontiers in pharmacology · 2024Review
- Platelet biology and function: plaque erosion vs. rupture.European heart journal · 2024Review
- Review
- MMP-2 Associates With Incident Heart Failure and Atrial Fibrillation: The ARIC Study.Circulation. Heart failure · 2023Article
- Identification of miR-143-3p as a diagnostic biomarker in gastric cancer.BMC medical genomics · 2023Article
- Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease.Mediators of inflammation · 2023Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPlatelets participate in atherogenesis with mechanisms not yet fully clarified. Vascular wall MMP-2 is involved in the arterial remodelling accompanying atherosclerosis. Platelets contain and release MMP-2 but no informations are available on its role in atherosclerotic lesion formation. METHODS AND
resultsWe generated double knockout mice lacking the LDL receptor and MMP-2 only in circulating blood cells showing that they develop significantly lesser femoral intima thickening after photochemical-induced arterial damage and atherosclerotic lesions in the aorta, measured by the en face method, after 4 months of atherogenic diet. Moreover, repeated transfusions of autologous-activated platelets in LDLR-/- mice on atherogenic diet significantly enhanced the extension of aortic atherosclerotic lesions while transfusion of activated platelets from MMP-2-/- mice did not. In vitro coincubation studies showed that platelet-derived MMP-2 plays a pivotal role in the development and progression of atherosclerosis through a complex cross-talk between activated platelets, monocyte/macrophages, and endothelial cells. Translational studies in patients with CAD and chronic HIV infection showed that platelet surface expression of MMP-2 highly significantly correlated with the degree of carotid artery stenosis.
conclusionWe show a previously unknown mechanism of the pathway through which platelets expressing MMP-2 trigger the initial phases of atherosclerosis and provide a mechanism showing that they activate endothelial PAR-1 triggering endothelial p38MAPK signalling and the expression of adhesion molecules. The development of drugs blocking selectively platelet MMP-2 or its expression may represent a new approach to the prevention of atherosclerosis.
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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.