ArticleCirculation2010
Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion injury.
Article in Circulation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 207 citations in OpenAlex.
- Titin cleavage alters the myocardial elastic network and remodels the heart.Nature cardiovascular research · 2026Article
- Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis.Nature cardiovascular research · 2026Article
- Quantification of a serum titin fragment reflects dystrophin restoration in mdx mice and disease severity in patients with dystrophinopathies.Journal of neuromuscular diseases · 2026Article
- Urinary N-terminal titin fragment concentration as a non-invasive biomarker of exercise-induced muscle damage in males and females.European journal of applied physiology · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- 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
- Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.Nature biomedical engineering · 2025Article
- Liposomal Delivery of Allolobophora caliginosa Coelomic Fluid Attenuates Myocardial Infarction by Suppressing Oxidative Damage, Inflammation, and Apoptosis.Applied biochemistry and biotechnology · 2025Article
- Phosphorylation of CRYAB induces a condensatopathy to worsen post-myocardial infarction left ventricular remodeling.The Journal of clinical investigation · 2025Article
- Oxidative stress initiates hemodynamic change in CKD-induced heart disease.Basic research in cardiology · 2024Article
- N-Terminomic Identification of Intracellular MMP-2 Substrates in Cardiac Tissue.Journal of proteome research · 2024Article
- Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.Biomedicines · 2024Article
- Is atrial fibrillation in HFpEF a distinct phenotype? Insights from multiparametric MRI and circulating biomarkers.BMC cardiovascular disorders · 2024Article
- Data-Independent Acquisition Proteomics and N-Terminomics Methods Reveal Alterations in Mitochondrial Function and Metabolism in Ischemic-Reperfused Hearts.Journal of proteome research · 2024Article
- The Utility of Urinary Titin to Diagnose and Predict the Prognosis of Acute Myocardial Infarction.International journal of molecular sciences · 2024Article
- An update of the molecular mechanisms underlying anthracycline induced cardiotoxicity.Frontiers in pharmacology · 2024Review
- Interleukin-1β activates matrix metalloproteinase-2 to alter lacrimal gland myoepithelial cell structure and function.Frontiers in ophthalmology · 2024Article
- The roles of intracellular proteolysis in cardiac ischemia-reperfusion injury.Basic research in cardiology · 2023Review
- Matrix metalloproteinase-2 proteolyzes mitofusin-2 and impairs mitochondrial function during myocardial ischemia-reperfusion injury.Basic research in cardiology · 2023Article
- Matrix metalloproteinases in coronary artery disease and myocardial infarction.Basic research in cardiology · 2023Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTitin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation in ischemia/reperfusion injury, proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction. METHODS AND
resultsImmunohistochemistry and confocal microscopy in rat and human hearts showed discrete colocalization between MMP-2 and titin in the Z-disk region of titin and that MMP-2 is localized mainly to titin near the Z disk of the cardiac sarcomere. Both purified titin and titin in skinned cardiomyocytes were proteolyzed when incubated with MMP-2 in a concentration-dependent manner, and this was prevented by MMP inhibitors. Isolated rat hearts subjected to ischemia/reperfusion injury showed cleavage of titin in ventricular extracts by gel electrophoresis, which was confirmed by reduced titin immunostaining in tissue sections. Inhibition of MMP activity with ONO-4817 prevented ischemia/reperfusion-induced titin degradation and improved the recovery of myocardial contractile function. Titin degradation was also reduced in hearts from MMP-2 knockout mice subjected to ischemia/reperfusion in vivo compared with wild-type controls.
conclusionMMP-2 localizes to titin at the Z-disk region of the cardiac sarcomere and contributes to titin degradation in myocardial ischemia/reperfusion injury.
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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.