ArticleMolecular metabolism2015
TIMP3 interplays with apelin to regulate cardiovascular metabolism in hypercholesterolemic mice.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Cocaine-Induced Cardiac Alterations: Histological and Immunohistochemical Post-Mortem Analysis.Diagnostics (Basel, Switzerland) · 2025Article
- Gene expression profiles, potential targets and treatments of cardiac remodeling.Molecular and cellular biochemistry · 2025Review
- Glucose-6-phosphate dehydrogenase deficiency accelerates arterial aging in diabetes.Acta diabetologica · 2024Article
- Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies.Biomedicines · 2023Review
- Is the Gut Microbiome Implicated in the Excess Risk of Hypertension Associated with Obstructive Sleep Apnea? A Contemporary Review.Antioxidants (Basel, Switzerland) · 2023Review
- Role of Stearoyl-CoA Desaturase 1 in Cardiovascular Physiology.International journal of molecular sciences · 2023Review
- TIMP3 induces gene expression partly through PI3K and their association with vascularization and heart rate.Frontiers in cardiovascular medicine · 2023Article
- CHOP Increases TRIB3-Dependent miR-208 Expression to Potentiate Vascular Smooth Muscle Cell Proliferation and Migration by Downregulating TIMP3 in Atherosclerosis.Cardiovascular drugs and therapy · 2022Article
- Construction and analysis of competing endogenous RNA network and patterns of immune infiltration in abdominal aortic aneurysm.Frontiers in cardiovascular medicine · 2022Article
- Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer.Cancers · 2021Review
- Apelin/APJ-Manipulated CaMKK/AMPK/GSK3Oxidative medicine and cellular longevity · 2021Article
- MicroRNA-221 promotes proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) by targeting tissue inhibitor of metalloproteinases-3 (TIMP3).Cardiovascular diagnosis and therapy · 2020Article
- Dare to Compare. Development of Atherosclerotic Lesions in Human, Mouse, and Zebrafish.Frontiers in cardiovascular medicine · 2020Review
- Apelin/APJ system: A potential therapeutic target for endothelial dysfunction-related diseases.Journal of cellular physiology · 2019Review
- Elevated 20-HETE in metabolic syndrome regulates arterial stiffness and systolic hypertension via MMP12 activation.Journal of molecular and cellular cardiology · 2018Article
- Screening key genes for abdominal aortic aneurysm based on gene expression omnibus dataset.BMC cardiovascular disorders · 2018Article
- Observational
- Allele-specific expression in the human heart and its application to postoperative atrial fibrillation and myocardial ischemia.Genome medicine · 2016Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTissue inhibitor of metalloproteinase 3 (TIMP3) is an extracellular matrix (ECM) bound protein, which has been shown to be downregulated in human subjects and experimental models with cardiometabolic disorders, including type 2 diabetes mellitus, hypertension and atherosclerosis. The aim of this study was to investigate the effects of TIMP3 on cardiac energy homeostasis during increased metabolic stress conditions.
methodsApoE(-/-)TIMP3(-/-) and ApoE(-/-) mice on a C57BL/6 background were subjected to telemetric ECG analysis and experimental myocardial infarction as models of cardiac stress induction. We used Western blot, qRT-PCR, histology, metabolomics, RNA-sequencing and in vivo phenotypical analysis to investigate the molecular mechanisms of altered cardiac energy metabolism.
resultsApoE(-/-)TIMP3(-/-) revealed decreased lifespan. Telemetric ECG analysis showed increased arrhythmic episodes, and experimental myocardial infarction by left anterior descending artery (LAD) ligation resulted in increased peri-operative mortality together with increased scar formation, ventricular dilatation and a reduction of cardiac function after 4 weeks in the few survivors. Hearts of ApoE(-/-)TIMP3(-/-) exhibited accumulation of neutral lipids when fed a chow diet, which was exacerbated by a high fat, high cholesterol diet. Metabolomics analysis revealed an increase in circulating markers of oxidative stress with a reduction in long chain fatty acids. Using whole heart mRNA sequencing, we identified apelin as a putative modulator of these metabolic defects. Apelin is a regulator of fatty acid oxidation, and we found a reduction in the levels of enzymes involved in fatty acid oxidation in the left ventricle of ApoE(-/-)TIMP3(-/-) mice. Injection of apelin restored the hitherto identified metabolic defects of lipid oxidation.
conclusionTIMP3 regulates lipid metabolism as well as oxidative stress response via apelin. These findings therefore suggest that TIMP3 maintains metabolic flexibility in the heart, particularly during episodes of increased cardiac stress.
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