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Vildagliptin reduces myocardial ischemia-induced arrhythmogenesis via modulating inflammatory responses and promoting expression of genes regulating mitochondrial biogenesis in rats with type-II diabetes

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Purpose

Fatal arrhythmias are one of the main manifestations of ischemic heart disease in diabetic patients. Here, we investigated the effect of pretreatment with vildagliptin on myocardial arrhythmias, inflammatory responses, and expression of genes regulating mitochondrial biogenesis following cardiac ischemic injury in type II diabetic male Wistar rats.

Methods

Chronic diabetes was modeled by a high-fat diet and low-dose streptozotocin method and lasted for 12 weeks. Vildagliptin (6 mg/dl) was orally administered during the last 4 weeks of the diabetic period. Then, rats’ hearts (n = 8/each group) were immediately isolated and transferred to the Langendorff apparatus, in which left anterior descending coronary artery was tightened for 35 min to induce regional ischemia. Electrocardiography was continuously recorded and myocardial arrhythmias were interpreted according to the Lambeth Convention. Inflammatory cytokines in left ventricular samples were measured using ELISA kits, and gene expression was assayed using real-time PCR.

Results

Diabetic groups showed increased incidence and duration of ventricular fibrillation (VF) than controls (P < 0.05). Pretreatment of diabetic rats with vildagliptin resulted in a significant decrease in number, duration, and severity of premature ventricular complexes (PVC), tachycardia (VT), and VF during ischemia, compared to non-treated diabetic group (P < 0.05). Additionally, vildagliptin significantly increased the expression of genes PGC-1α, SIRT-1, and NRF-2 and reduced the levels of myeloperoxidase, creatine kinase release, and myocardial content of TNF-α and IL-1β in nondiabetic and diabetic rats as compared to corresponding controls (P < 0.01–0.05).

Conclusion

Vildagliptin preconditioning reduced the occurrence and severity of fatal ventricular arrhythmias induced by myocardial ischemia in type II diabetic rats through increased activity of mitochondrial biogenesis-regulating genes and reduction of inflammatory reactions.

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Abbreviations

VF :

Ventricular fibrillation

VT :

Ventricular tachycardia

VB :

Ventricular bigeminy

VS :

Ventricular salvos

VPB :

Single ventricular premature beat

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Authors and Affiliations

  1. Department of Cardiology, Jiangxi Provincial People’s Hospital affiliated to Nanchang University, 330006, Jiangxi, China

    Qin Yang

  2. Department of General Medicine, Jiangxi Provincial People’s Hospital affiliated to Nanchang University, 330006, Jiangxi, China

    Wenwei Ai & Su Wu

  3. Department of Geriatric, Jiangxi Provincial People’s Hospital affiliated to Nanchang University, 330006, Jiangxi, China

    Lei Nie

  4. Department of Cardiology, Harbin Fifth Hospital, Harbin, Heilongjiang, 330006, China

    Chen Yan

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  1. Qin Yang
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  2. Wenwei Ai
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  3. Lei Nie
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  4. Chen Yan
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  5. Su Wu
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Contributions

All authors contributed to the study conception and design, material preparation, data collection, and analysis. Su Wu and Qin Yang wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Su Wu.

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Yang, Q., Ai, W., Nie, L. et al. Vildagliptin reduces myocardial ischemia-induced arrhythmogenesis via modulating inflammatory responses and promoting expression of genes regulating mitochondrial biogenesis in rats with type-II diabetes. J Interv Card Electrophysiol 59, 517–526 (2020). https://doi.org/10.1007/s10840-019-00679-9

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