ArticleAmerican journal of physiology. Cell physiology2008
Downregulation of connexin40 is associated with coronary endothelial cell dysfunction in streptozotocin-induced diabetic mice.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 77 citations in OpenAlex.
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- Review
- Chronic Stress and Gonadectomy Affect the Expression of Cx37, Cx40 and Cx43 in the Spinal Cord.Life (Basel, Switzerland) · 2021Article
- HuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes.JCI insight · 2021Article
- Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine.Journal of cardiovascular development and disease · 2021Review
- Chronic Hypoxia Decreases Endothelial Connexin 40, Attenuates Endothelium-Dependent Hyperpolarization-Mediated Relaxation in Small Distal Pulmonary Arteries, and Leads to Pulmonary Hypertension.Journal of the American Heart Association · 2020Article
- Vascular smooth muscle cell phenotypic transition regulates gap junctions of cardiomyocyte.Heart and vessels · 2020Article
- Overexpression of p53 due to excess protein O-GlcNAcylation is associated with coronary microvascular disease in type 2 diabetes.Cardiovascular research · 2020Article
- Chloroquine differentially modulates coronary vasodilation in control and diabetic mice.British journal of pharmacology · 2020Article
- Endothelium-Dependent Hyperpolarization (EDH) in Diabetes: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2019Review
- Pulmonary vascular dysfunction in metabolic syndrome.The Journal of physiology · 2019Review
- Angiopoietin-1 Promotes the Integrity of Neovascularization in the Subcutaneous Matrigel of Type 1 Diabetic Rats.BioMed research international · 2019Article
- Overexpression of hexokinase 2 reduces mitochondrial calcium overload in coronary endothelial cells of type 2 diabetic mice.American journal of physiology. Cell physiology · 2018Article
- Role of the endothelial caveolae microdomain in shear stress-mediated coronary vasorelaxation.The Journal of biological chemistry · 2017Article
- Connexin channel and its role in diabetic retinopathy.Progress in retinal and eye research · 2017Review
- Obesity-induced vascular inflammation involves elevated arginase activity.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Article
- Mitochondrial connexin40 regulates mitochondrial calcium uptake in coronary endothelial cells.American journal of physiology. Cell physiology · 2017Article
- Regulation of Coronary Blood Flow.Comprehensive Physiology · 2017Review
- Hypoxia-induced pulmonary hypertension in type 2 diabetic mice.Pulmonary circulation · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial cells (ECs) play a major role in regulating vascular tone and in revascularization. There is increasing evidence showing endothelial dysfunction in diabetes, although little is known about the contribution of connexins (Cxs) to vascular complications in the diabetic heart. This study was designed to investigate the role of Cxs in coronary endothelial dysfunction in diabetic mice. Coronary ECs isolated from diabetic mice exhibit lowered protein levels of Cx37 and Cx40 (but not Cx43) and a loss of gap junction intercellular communication (GJIC). Vasodilatation induced by the assumed contribution of EC-dependent hyperpolarization was significantly reduced in the diabetic coronary artery (CA). Cx40-specific inhibitory peptide (40)GAP27 strongly attenuated endothelium-dependent relaxation in diabetic CA at the concentration that does not affect the relaxation in control CA, suggesting that the total amount of Cx40 is lower in diabetic CA than in control CA. In diabetic mice, coronary capillary density was significantly decreased in vivo. In vitro, GJIC inhibitor attenuated the ability of EC capillary network formation. High-glucose treatment caused a decrease in Cx40 protein expression in ECs and impaired endothelial capillary network formation, which was restored by Cx40 overexpression. Furthermore, we found that the hyperglycemia-induced decrease in Cx40 was associated with inhibited protein expression of Sp1, a transcriptional factor that regulates Cx40 expression. These data suggest that downregulation of Cx40 protein expression and resultant inhibition of GJIC contribute to coronary vascular dysfunction in diabetes.
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