ArticleCardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
Human cardiac fibroblast extracellular matrix remodeling: dual effects of tissue inhibitor of metalloproteinase-2.
Article in Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Extracellular Matrix Remodeling during Left Ventricular Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2020Pooled it
- Hidradenitis suppurativa: epidemiology, diagnosis, molecular pathogenesis and therapy.Molecular biomedicine · 2026Review
- Cellular and molecular cross-talk in atrial fibrillation: The role of non-cardiomyocytes in creating an arrhythmogenic substrate.The Journal of physiology · 2026Review
- The Continuing Saga of Tissue Inhibitor of Metalloproteinase 2: Emerging Roles in Tissue Homeostasis and Cancer Progression.The American journal of pathology · 2023Review
- Improving hard metal implant and soft tissue integration by modulating the "inflammatory-fibrous complex" response.Bioactive materials · 2023Article
- Canadian Contributions in Fibroblast Biology.Cells · 2022Review
- Developmental dynamics of the neural crest-mesenchymal axis in creating the thymic microenvironment.Science advances · 2022Article
- A deep learning approach to identify and segment alpha-smooth muscle actin stress fiber positive cells.Scientific reports · 2021Article
- Dye-Mediated Photo-Oxidation Biomaterial Fixation: Analysis of Bioinductivity and Mechanical Properties of Bovine Pericardium for Use in Cardiac Surgery.International journal of molecular sciences · 2021Article
- Tumor necrosis factor α, protein gene product 9.5, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 presence in congenital intra-abdominal adhesions in children under one year of age.Archives of medical science : AMS · 2021Article
- Modulating the Biomechanical Properties of Engineered Connective Tissues by Chitosan-Coated Multiwall Carbon Nanotubes.International journal of nanomedicine · 2021Article
- Extracellular Vesicles as Therapeutic Agents for Cardiac Fibrosis.Frontiers in physiology · 2020Review
- MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1.BMC molecular biology · 2019Article
- Sustained Release of a Peptide-Based Matrix Metalloproteinase-2 Inhibitor to Attenuate Adverse Cardiac Remodeling and Improve Cardiac Function Following Myocardial Infarction.Biomacromolecules · 2017Article
- Effects and mechanism of adenovirus-mediated phosphatase and tension homologue deleted on chromosome ten gene on collagen deposition in rat liver fibrosis.World journal of gastroenterology · 2017Article
- Temporal analysis of blood-brain barrier disruption and cerebrospinal fluid matrix metalloproteinases in rhesus monkeys subjected to transient ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Association of white blood cell counts with left ventricular mass index in hypertensive patients undergoing anti-hypertensive drug therapy.Experimental and therapeutic medicine · 2017Article
- Matrix metalloproteinases in exercise and obesity.Vascular health and risk management · 2016Review
- Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated extracellular matrix remodeling.Journal of translational medicine · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveTissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of matrix metalloproteinases (MMPs) that attenuates maladaptive cardiac remodeling in ischemic heart failure. We examined the effects of TIMP-2 on human cardiac fibroblast activation and extracellular matrix (ECM) remodeling.
methodsHuman cardiac fibroblasts within a three-dimensional collagen matrix were assessed for phenotype conversion, ECM architecture and key molecular regulators of ECM remodeling after differential exposure to TIMP-2 and Ala+TIMP-2 (a modified TIMP-2 analogue devoid of MMP inhibitory activity).
resultsTIMP-2 induced opposite effects on human cardiac fibroblast activation and ECM remodeling depending on concentration. TIMP-2 activated fibroblasts into contractile myofibroblasts that remodeled ECM. At higher concentrations (>10 nM), TIMP-2 inhibited fibroblast activation and prevented ECM remodeling. As compared to profibrotic cytokine transforming growth factor (TGF)-beta1, TIMP-2 activated fibroblasts and remodeled ECM without a net accumulation of matrix elements. TIMP-2 increased total protease activity as compared to TGF-beta1. Ala+TIMP-2 exposure revealed that the actions of TIMP-2 on cardiac fibroblast activation are independent of its effects on MMP inhibition. In the presence of GM6001, a broad-spectrum MMP inhibitor, TIMP-2-mediated ECM contraction was completely abolished, indicating that TIMP-2-mediated fibroblast activation is MMP dependent.
conclusionTIMP-2 functions in a contextual fashion such that the effect on cardiac fibroblasts depends on the tissue microenvironment. These observations highlight potential clinical challenges in using TIMP-2 as a therapeutic strategy to attenuate postinjury cardiac remodeling.
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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.