ArticleBritish journal of pharmacology2012
Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Effect of High Intensity Interval Training on Matrix Metalloproteinases in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy.Scientific reports · 2020Trial
- Apiotrichum-Centered Fungal Interaction Network Disturbance Correlates With Increased Arterial Stiffness.Aging cell · 2026Article
- The Hidden Price of Plenty: Oxidative Stress and Calorie-Induced Cardiometabolic Dysfunction.Life (Basel, Switzerland) · 2025Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease.Mediators of inflammation · 2023Review
- Theories and Molecular Basis of Vascular Aging: A Review of the Literature from VascAgeNet Group on Pathophysiological Mechanisms of Vascular Aging.International journal of molecular sciences · 2022Review
- The Pathological Links between Adiposity and the Carpal Tunnel Syndrome.Current issues in molecular biology · 2022Review
- Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation.The Journal of clinical investigation · 2022Article
- MMPs and TIMPs levels are correlated with anthropometric parameters, blood pressure, and endothelial function in obesity.Scientific reports · 2021Article
- Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations.Biomolecules · 2021Review
- CD44, a Predominant Protein in Methylglyoxal-Induced Secretome of Muscle Cells, is Elevated in Diabetic Plasma.ACS omega · 2020Article
- Article
- The mechanisms underlying fructose-induced hypertension: a review.Journal of hypertension · 2015Review
- Matrix metalloproteinases promote arterial remodeling in aging, hypertension, and atherosclerosis.Hypertension (Dallas, Tex. : 1979) · 2015Review
- Blockade of MMP14 activity in murine breast carcinomas: implications for macrophages, vessels, and radiotherapy.Journal of the National Cancer Institute · 2015Article
- Effects of monocyte-endothelium interactions on the expression of type IV collagenases in monocytes.Experimental and therapeutic medicine · 2015Article
- Proteolytic receptor cleavage in the pathogenesis of blood rheology and co-morbidities in metabolic syndrome. Early forms of autodigestion.Biorheology · 2015Review
- Antioxidant response of osteoblasts to doxycycline in an inflammatory model induced by C-reactive protein and interleukin-6.Infectious disorders drug targets · 2014Article
- Study of the correlations among some parameters of the oxidative status, gelatinases, and their inhibitors in a group of subjects with metabolic syndrome.Mediators of inflammation · 2014Article
- Combined subthreshold dose inhibition of myosin light chain phosphorylation and MMP-2 activity provides cardioprotection from ischaemic/reperfusion injury in isolated rat heart.British journal of pharmacology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeInsulin resistance is often found to be associated with high blood pressure. We propose that in insulin-resistant hypertension, endothelial dysfunction is the consequence of increased activity of vascular MMP-2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we hypothesized that MMP-2 impairs endothelial function by proteolytic degradation of endothelial NOS (eNOS) or its cofactor, heat shock protein 90 (HSP90). EXPERIMENTAL APPROACH: We tested our hypothesis in bovine coronary artery endothelial cells and fructose-fed hypertensive rats (FHR), a model of acquired systolic hypertension and insulin resistance. KEY
resultsTreatment of FHRs with the MMP inhibitor doxycycline, preserved endothelial function as well as prevented the development of hypertension, suggesting that MMPs impair endothelial function. Furthermore, incubating endothelial cells in vitro with a recombinant MMP-2 decreased NO production in a dose-dependent manner. Using substrate cleavage assays and immunofluorescence microscopy studies, we found that MMP-2 not only cleaves and degrades HSP90, an eNOS cofactor but also co-localizes with both eNOS and HSP90 in endothelial cells, suggesting that MMPs functionally interact with the eNOS system. Treatment of FHRs with doxycycline attenuated the decrease in eNOS and HSP90 expression but did not improve insulin sensitivity. CONCLUSIONS AND IMPLICATIONS: Our data suggest that increased activity of MMP-2 in FHRs impairs endothelial function and promotes hypertension. Inhibition of MMP-2 could be a potential therapeutic strategy for the management of hypertension.
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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 Socratic graph.