ArticleRedox biology2018
Matrix metalloproteinase-2-induced epidermal growth factor receptor transactivation impairs redox balance in vascular smooth muscle cells and facilitates vascular contraction.
Article in Redox biology, 2018. 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, 43 citations in OpenAlex.
- Fast-Food Component-Induced Epigenetic Modifications Modulate Immunotherapy in Metastatic Breast Cancer.ACS omega · 2026Article
- Oxidative Stress and Redox Imbalance inInternational journal of molecular sciences · 2026Review
- Neoagarotetraose from Marine Red Algae Attenuates Hypertensive Vascular Remodeling by Targeting FoxO4 to Inhibit Mitochondrial Superoxide Generation.Journal of agricultural and food chemistry · 2026Article
- Correlation of Oxidative Stress Markers and Nuclear Abnormalities with Clinical Parameters in Individuals with Periodontitis.Dentistry journal · 2026Article
- Article
- siRNA-mediated inhibition of NTT-MMP-2 reduces oxidative stress and apoptotic signaling in an ex vivo model of ischemia/reperfusion injury.Scientific reports · 2025Article
- Oxidative Stress, MicroRNAs, and Long Non-Coding RNAs in Osteoarthritis Pathogenesis: Cross-Talk and Molecular Mechanisms Involved.International journal of molecular sciences · 2025Review
- Inhibitors of gastric acid secretion increase oxidative stress and matrix metalloproteinase-2 activity leading to vascular remodeling.Molecular and cellular biochemistry · 2024Article
- The role of oxidative stress in aortic dissection: a potential therapeutic target.Frontiers in cardiovascular medicine · 2024Review
- Unveiling the power of flavonoids: A dynamic exploration of their impact on cancer through matrix metalloproteinases regulation.BioMedicine · 2024Review
- Epigenetic modifications and fetal programming: Molecular mechanisms to control hypertension inheritance.Biochemical pharmacology · 2023Review
- "K-Powder" Exposure during Adolescence Elicits Psychiatric Disturbances Associated with Oxidative Stress in Female Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- BmooMPα-I, a Metalloproteinase Isolated fromToxins · 2022Article
- Article
- Doxycycline Decreases Atherosclerotic Lesions in the Aorta ofInternational journal of molecular sciences · 2022Article
- The Molecular Mechanism of Aerobic Exercise Improving Vascular Remodeling in Hypertension.Frontiers in physiology · 2022Review
- Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations.Biomolecules · 2021Review
- The Role of Epidermal Growth Factor Receptor Family of Receptor Tyrosine Kinases in Mediating Diabetes-Induced Cardiovascular Complications.Frontiers in pharmacology · 2021Review
- Extracellular matrix dynamics in vascular remodeling.American journal of physiology. Cell physiology · 2020Review
- Nucleolin promotes Ang II-induced phenotypic transformation of vascular smooth muscle cells by regulating EGF and PDGF-BB.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased reactive oxygen species (ROS) formation may enhance matrix metalloproteinase (MMP)-2 activity and promote cardiovascular dysfunction. We show for the first time that MMP-2 is upstream of increased ROS formation and activates signaling mechanisms impairing redox balance. Incubation of vascular smooth muscle cells (VSMC) with recombinant MMP-2 increased ROS formation assessed with dihydroethidium (DHE) by flow cytometry. This effect was blocked by the antioxidant apocynin or by polyethylene glycol-catalase (PEG-catalase), and by MMP inhibitors (doxycycline or GM6001). Next, we showed in HEK293 cells that MMP-2 transactivates heparin-binding epidermal growth factor (HB-EGF) leading to EGF receptor (EGFR) activation and increased ROS concentrations. This effect was prevented by the EGFR kinase inhibitor Ag1478, and by phospholipase C (PLC) or protein kinase C (PKC) inhibitors (A778 or chelerythrine, respectively), confirming the involvement of EGFR pathway in MMP-2-induce responses. Next, we showed that intraluminal exposure of aortas to MMP-2 increased vascular MMP-2 levels detected by immunofluorescence and gelatinolytic activity (by in situ zimography) in association with increased ROS formation. This effect was inhibited by MMP inhibitors (phenanthroline or doxycycline) and by apocynin or PEG-catalase. MMP-2 also increased aortic contractility to phenylephrine and this effect was prevented by MMP inhibitor GM6001 and by apocynin or PEG-catalase, showing again that increased ROS formation mediates functional effects of MMP-2. These results show that MMP-2 activates the EGFR and triggers downstream signaling pathways increasing ROS formation and promoting vasoconstriction. These findings may have various implications for cardiovascular diseases.
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