ArticleAlcoholism, clinical and experimental research2014
Alcohol modulation of cardiac matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs favors collagen accumulation.
Article in Alcoholism, clinical and experimental research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
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- Concurrent Chronic-Plus-Binge Alcohol Consumption and Nicotine Vaping Alter the Cardiac Ventricular Proteome in a Preclinical Mouse Model.International journal of molecular sciences · 2026Article
- Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities.Comprehensive Physiology · 2025Review
- Blockade of thromboxane A2 signaling attenuates ethanol-induced myocardial inflammatory response in mice.Alcohol, clinical & experimental research · 2024Article
- Abstinence Restores Cardiac Function in Mice with Established Alcohol-Induced Cardiomyopathy.Cells · 2023Article
- ADSCs-derived exosomes ameliorate hepatic fibrosis by suppressing stellate cell activation and remodeling hepatocellular glutamine synthetase-mediated glutamine and ammonia homeostasis.Stem cell research & therapy · 2022Article
- Alcohol Dependence in Rats Is Associated with Global Changes in Gene Expression in the Central Amygdala.Brain sciences · 2021Article
- Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway.Molecular medicine reports · 2021Article
- Myocardial tissue and metabolism characterization in men with alcohol consumption by cardiovascular magnetic resonance and 11C-acetate PET/CT.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2020Article
- Inflammatory cardiac fibroblast phenotype underlies chronic alcohol-induced cardiac atrophy and dysfunction.Life sciences · 2020Article
- The peptide compound urantide regulates collagen metabolism in atherosclerotic rat hearts and inhibits the JAK2/STAT3 pathway.Molecular medicine reports · 2020Article
- Therapeutic Targets for the Treatment of Cardiac Fibrosis and Cancer: Focusing on TGF-β Signaling.Frontiers in cardiovascular medicine · 2020Review
- N-Acetylcysteine prevents the decreases in cardiac collagen I/III ratio and systolic function in neonatal mice with prenatal alcohol exposure.Toxicology letters · 2019Article
- Prenatal Alcohol Exposure Causes Adverse Cardiac Extracellular Matrix Changes and Dysfunction in Neonatal Mice.Cardiovascular toxicology · 2019Article
- Cardiac Toxicity From Ethanol Exposure in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Molecular mechanisms in the pathogenesis of N-nitrosodimethylamine induced hepatic fibrosis.Cell death & disease · 2019Review
- Inhibitor of lysyl oxidase improves cardiac function and the collagen/MMP profile in response to volume overload.American journal of physiology. Heart and circulatory physiology · 2018Article
- Exposure to chronic alcohol accelerates development of wall stress and eccentric remodeling in rats with volume overload.Journal of molecular and cellular cardiology · 2016Article
- Alcohol Vapor Inhalation as a Model of Alcohol-Induced Organ Disease.Alcoholism, clinical and experimental research · 2016Article
- Cardioprotective effects of lysyl oxidase inhibition against volume overload-induced extracellular matrix remodeling.Experimental biology and medicine (Maywood, N.J.) · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic alcohol consumption has been shown in human and animal studies to result in collagen accumulation, myocardial fibrosis, and heart failure. Cardiac fibroblasts produce collagen and regulate extracellular matrix (ECM) homeostasis through the synthesis and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), with the balance of MMPs/TIMPs determining the rate of collagen turnover. Dynamic changes of MMP and TIMP expression were reported in alcohol-induced hepatic fibrosis; however, the effect of alcohol on MMP/TIMP balance in the heart and cardiac fibroblasts is unknown. We hypothesized that alcohol exposure alters cardiac fibroblast MMP and TIMP expression to promote collagen accumulation in the heart.
methodsCardiac fibroblasts isolated from adult rats were cultured in the presence of alcohol (12.5 to 200 mM) for 48 hours. MMP, TIMP, and collagen type I and III expression were assayed by Western blot analysis. Hydroxyproline (HPro) was used as a marker of collagen production. The in vivo cardiac effects of ethanol (EtOH) were determined using rats exposed to EtOH vapor for 2 weeks, resulting in blood alcohol levels of 150 to 200 mg/dl. Cardiac collagen volume fraction (CVF), as well as MMP, TIMP, and collagen expression, was assessed.
resultsEtOH-exposed rats exhibited up-regulation of TIMP-1, TIMP-3 and TIMP-4 in the heart, with no significant increases in MMPs. Cardiac fibroblasts exhibited transformation to a profibrotic phenotype following exposure to alcohol. These changes were reflected by increased α-smooth muscle actin and collagen I and III expression, as well as increased collagen secretion. In vivo EtOH exposure also produced fibrosis, indicated by increased CVF and expression of collagens.
conclusionsAlcohol exposure modulates cardiac fibroblast MMP/TIMP expression favoring a profile associated with collagen accumulation. Our data suggest that this disrupted MMP/TIMP profile may contribute to the development of myocardial fibrosis and cardiac dysfunction resulting from chronic alcohol abuse.
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