ArticleJournal of molecular and cellular cardiology2018
Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Platelet-derived serotonin epigenetically programs macrophage alternative activation to orchestrate type 2 airway inflammation.Cellular & molecular immunology · 2026Article
- Human Transglutaminases: Updated Insights into Activation Mechanisms, Allosteric Regulation and Disease.International journal of molecular sciences · 2026Review
- Left ventricular hypertrophy and myocardial fibrosis in heart failure with preserved ejection fraction: mechanisms and treatment.European heart journal · 2026Review
- Transglutaminase 2 in human peritoneal dialysis-related peritoneal injury.Physiological reports · 2025Article
- A Review on the Natural Products in Treatment of Diabetic Cardiomyopathy (DCM).Reviews in cardiovascular medicine · 2024Review
- Role of platelet factor 4 in arteriovenous fistula maturation failure: What do we know so far?The journal of vascular access · 2024Review
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- Cystamine reduces vascular stiffness in Western diet-fed female mice.American journal of physiology. Heart and circulatory physiology · 2022Article
- The heart under pressure: immune cells in fibrotic remodeling.Current opinion in physiology · 2022Article
- Review
- Cardiac fibrosis.Cardiovascular research · 2021Review
- Cross your heart? Collagen cross-links in cardiac health and disease.Cellular signalling · 2021Review
- Glycolysis regulated transglutaminase 2 activation in cardiopulmonary fibrogenic remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Increased Transglutaminase 2 Expression and Activity in Rodent Models of Obesity/Metabolic Syndrome and Aging.Frontiers in physiology · 2020Article
- Mechanisms of cardiac collagen deposition in experimental models and human disease.Translational research : the journal of laboratory and clinical medicine · 2019Review
- The Extracellular Matrix in Ischemic and Nonischemic Heart Failure.Circulation research · 2019Review
- Tissue Transglutaminase-Mediated AT1 Receptor Sensitization Underlies Pro-inflammatory Cytokine LIGHT-Induced Hypertension.American journal of hypertension · 2019Article
- Role of Renin-Angiotensin-Aldosterone System Activation in Promoting Cardiovascular Fibrosis and Stiffness.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor.Cell death & disease · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction.
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Registered trials
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