ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Apelin gene therapy increases myocardial vascular density and ameliorates diabetic cardiomyopathy via upregulation of sirtuin 3.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 112 citations in OpenAlex.
- α7-nAChR Activation is Associated with Attenuation of Cardiac Fibrosis in Ischemic Cardiomyopathy via SIRT3-Dependent Modulation of EndMT.Journal of cardiovascular translational research · 2026Article
- Exerkines in Cardiovascular-Kidney-Metabolic Syndrome: An Integrative Framework for Mechanisms and Therapeutic Implications-A Narrative Review.Reviews in cardiovascular medicine · 2026Review
- Context‑dependent duality of the apelin/elabela‑APJ system in diabetes and its complications (Review).International journal of molecular medicine · 2026Review
- Beyond Leptin and Adiponectin: The Diverse Roles of Adipokines in the Myocardial Hypertrophic Process and Heart Failure and Their Potential Contribution in Obesity.International journal of molecular sciences · 2025Review
- EGLN1 inhibition reverses angiogenesis impairment in hyperglycemia by activating autophagy.Scientific reports · 2025Article
- Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives.Molecular and cellular biochemistry · 2025Review
- Estrogen Inhibits the Phenotypic Switching of Vascular Smooth Muscle Cells through ER-α/CREB in Aortic Dissection.ACS omega · 2025Article
- Exercise in Diabetic Cardiomyopathy: Its Protective Effects and Molecular Mechanism.International journal of molecular sciences · 2025Review
- Effects of exercise intensity and diet on cardiac tissue structure and FGF21/β-Klotho signaling in type 2 diabetic mice: a comparative study of HFD and HFD + STZ induced type 2 diabetes models in mice.Diabetology & metabolic syndrome · 2025Article
- Exploring the key target molecules of angiogenesis in diabetic cardiomyopathy based on bioinformatics analysis.Frontiers in endocrinology · 2025Article
- Effects of apelin on neonatal brain neurogenesis in L-NAME-induced maternal preeclampsia.Scientific reports · 2024Article
- Unraveling the Complex Molecular Interplay and Vascular Adaptive Changes in Hypertension-Induced Kidney Disease.Biomedicines · 2024Article
- p53 Acetylation Exerts Critical Roles in Pressure Overload-Induced Coronary Microvascular Dysfunction and Heart Failure in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.Journal of thrombosis and thrombolysis · 2023Review
- Sirtuin-3-Mediated Cellular Metabolism Links Cardiovascular Remodeling with Hypertension.Biology · 2023Review
- Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms.Cardiovascular diabetology · 2023Review
- Potential clinical biomarkers and perspectives in diabetic cardiomyopathy.Diabetology & metabolic syndrome · 2023Review
- Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice.Biomedicines · 2023Review
- Review
- Sirtuin 3 Dependent and Independent Effects of NADAntioxidants (Basel, Switzerland) · 2022Article
6 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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Abstract
Microvascular insufficiency contributes to cardiac hypertrophy and worsens heart dysfunction in diabetic cardiomyopathy. Our recent study shows that apelin may protect ischemic heart failure via upregulation of sirtuin 3 (Sirt3) and angiogenesis. This study investigated whether apelin promotes angiogenesis and ameliorates diabetic cardiomyopathy via activation of Sirt3. Wild-type (WT) and diabetic db/db mice were administrated with adenovirus-apelin to overexpressing apelin. In WT mice, overexpression of apelin increased Sirt3, VEGF/VEGFR2, and angiopoietin-1 (Ang-1)/Tie-2 expression in the heart. In vitro, treatment of endothelial cells (EC) with apelin increased VEGF and Ang-1 expression. In EC isolated from Sirt3KO mice, however, apelin treatment did not upregulate VEGF and Ang-1 expression. Moreover, apelin-induced angiogenesis was diminished in Sirt3KO mice. In db/db mice, the basal levels of apelin and Sirt3 expression were significantly reduced in the heart. This was accompanied by a significant reduction of capillary and arteriole densities in the heart. Overexpression of apelin increased Sirt3, VEGF/VEGFR2, and Ang-1/Tie-2 expression together with improved vascular density in db/db mice. Overexpression of apelin further improved cardiac function in db/db mice. Treatment with apelin significantly attenuated high glucose (HG)-induced reactive oxygen species (ROS) formation and EC apoptosis. The protection of apelin against HG-induced ROS formation and EC apoptosis was diminished in Sirt3KO-EC. We conclude that apelin gene therapy increases vascular density and alleviates diabetic cardiomyopathy by a mechanism involving activation of Sirt3 and upregulation of VEGF/VEGFR2 and Ang-1/Tie-2 expression.
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