nach oben

Journal of Interventional Cardiac Electrophysiology

Erschienen in:

18.12.2019 | Ventricular Tachycardia

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

verfasst von: Qin Yang, Wenwei Ai, Lei Nie, Chen Yan, Su Wu

Erschienen in: Journal of Interventional Cardiac Electrophysiology | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

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.

Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diab. 2015;6:1246–58. https://doi.org/10.4239/wjd.v6.i13.1246.CrossRef

Saeid F, Aniseh J, Reza B, Manouchehr VS. Signaling mediators modulated by cardioprotective interventions in healthy and diabetic myocardium with ischaemia–reperfusion injury. Eur J Prev Cardiol. 2018;25:1463–81. https://doi.org/10.1177/2047487318756420.CrossRefPubMed

Severino P, D’Amato A, Netti L, Pucci M, Infusino F, Maestrini V, et al. Myocardial Ischemia and Diabetes Mellitus: Role of Oxidative Stress in the Connection between Cardiac Metabolism and Coronary Blood Flow. J Diabetes Res. 2019;(9489826). https://doi.org/10.1155/2019/9489826.

Neri M, Riezzo I, Pascale N, Pomara C, Turillazzi E. Ischemia/reperfusion injury following acute myocardial infarction: a critical issue for clinicians and forensic pathologists. Mediat Inflamm. 2017;7018393. https://doi.org/10.1155/2017/7018393.

Badalzadeh R, Azimi A, Alihemmati A, Yousefi B. Chronic type-I diabetes could not impede the anti-inflammatory and anti-apoptotic effects of combined postconditioning with ischemia and cyclosporine a in myocardial reperfusion injury. J Physiol Biochem. 2017;73(1):111–20. https://doi.org/10.1007/s13105-016-0530-4.CrossRefPubMed

Mollenhauer M, Friedrichs K, Lange M, Gesenberg J, Remane L, Kerkenpaß C, et al. Myeloperoxidase mediates Postischemic Arrhythmogenic ventricular remodeling. Circ Res. 2017;121(1):56–70. https://doi.org/10.1161/CIRCRESAHA.117.310870.CrossRefPubMedPubMedCentral

Song J, Yang R, Yang J, Zhou L. Mitochondrial dysfunction-associated Arrhythmogenic substrates in diabetes mellitus. Front Physiol. 2018;9:1670. https://doi.org/10.3389/fphys.2018.01670.CrossRefPubMedPubMedCentral

Fernandez-Marcos PJ, Auwerx J. Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr. 2011;93(4):884S–90S. https://doi.org/10.3945/ajcn.110.001917.CrossRefPubMedPubMedCentral

Mohamed JS1, Hajira A, Pardo PS, Boriek AM. MicroRNA-149 inhibits PARP-2 and promotes mitochondrial biogenesis via SIRT-1/PGC-1α network in skeletal muscle. Diabetes. 2014;63(5):1546–59. https://doi.org/10.2337/db13-1364.CrossRefPubMed

10.

Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. 2015;88:179–88. https://doi.org/10.1016/j.freeradbiomed.2015.04.036.CrossRefPubMedPubMedCentral

11.

Bekiari E, Rizava C, Athanasiadou E, Papatheodorou K, Liakos A, Karagiannis T, et al. Systematic review and meta-analysis of vildagliptin for treatment of type 2 diabetes. Endocrine. 2016;52(3):458–80. https://doi.org/10.1007/s12020-015-0841-1.CrossRefPubMed

12.

Williams R, de Vries F, Kothny W, Serban C, Lopez-Leon S, Chu C, et al. Cardiovascular safety of vildagliptin in patients with type 2 diabetes: a European multi-database, non-interventional post-authorization safety study. Diabetes Obes Metab. 2017;19(10):1473–8. https://doi.org/10.1111/dom.12951.CrossRefPubMed

13.

Bayrami G, Karimi P, Agha-Hosseini F, Feyzizadeh S, Badalzadeh R. Effect of ischemic Postconditioning on myocardial function and infarct size following reperfusion injury in diabetic rats pretreated with Vildagliptin. J Cardiovasc Pharmacol Ther. 2018;23(2):174–83. https://doi.org/10.1177/1074248417729881.CrossRefPubMed

14.

Apaijai N, Pintana H, Chattipakorn SC, Chattipakorn N. Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin-resistant rats. Br J Pharmacol. 2013;169(5):1048–57. https://doi.org/10.1111/bph.12176.CrossRefPubMedPubMedCentral

15.

Bayrami G, Alihemmati A, Karimi P. Combination of vildagliptin and ischemic postconditioning in diabetic hearts as a working strategy to reduce myocardial reperfusion injury by restoring mitochondrial function and autophagic activity. Adv Pharm Bull. 2018;8(2):319–29. https://doi.org/10.15171/apb.2018.037.CrossRefPubMedPubMedCentral

16.

Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005;52(4):313–20. https://doi.org/10.1016/j.phrs.2005.05.004.CrossRefPubMed

17.

Najafi M, Noroozi E, Javadi A, Badalzadeh R. Anti-arrhythmogenic and anti-inflammatory effects of troxerutin in ischemia/reperfusion injury of diabetic myocardium. Biomed Pharmacother. 2018;102:385–91. https://doi.org/10.1016/j.biopha.2018.03.047.CrossRefPubMed

18.

Bhar-Amato J, Davies W, Agarwal S. Ventricular arrhythmia after acute myocardial infarction: 'the perfect storm'. Arrhythm Electrophysiol Rev. 2017;6(3):134–9. https://doi.org/10.15420/aer.2017.24.1.CrossRefPubMedPubMedCentral

19.

Koektuerk B, Aksoy M, Horlitz M, Bozdag-Turan I, Turan RG. Role of diabetes in heart rhythm disorders. World J Diabetes. 2016;7(3):45–9. https://doi.org/10.4239/wjd.v7.i3.45.CrossRefPubMedPubMedCentral

20.

Korantzopoulos P, Letsas KP, Tse G, Fragakis N, Goudis CA, Liu T. Inflammation and atrial fibrillation: a comprehensive review. J Arrhythm. 2018;34(4):394–401. https://doi.org/10.1002/joa3.12077.CrossRefPubMedPubMedCentral

21.

Lazzerini PE, Laghi-Pasini F, Boutjdir M, Capecchi PL. Cardioimmunology of arrhythmias: the role of autoimmune and inflammatory cardiac channelopathies. Nat Rev Immunol. 2019 Jan;19(1):63–4. https://doi.org/10.1038/s41577-018-0098-z.CrossRefPubMed

22.

Saini HK, Xu Y-J, Zhang M, Liu PP, Kirshenbaum LA, Dhalla NS. Role of tumour necrosis factor-alpha and other cytokines in ischemia-reperfusion-induced injury in the heart. Exp Clin Cardiol. 2005;10(4):213–22.PubMedPubMedCentral

23.

Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023. https://doi.org/10.1038/sigtrans.2017.23.CrossRefPubMedPubMedCentral

24.

Anatoliotakis N, Deftereos S, Bouras G, Giannopoulos G, Tsounis D, Angelidis C, et al. Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease. Curr Top Med Chem. 2013;13(2):115–38.CrossRef

25.

Govender J, Loos B, Marais E, Engelbrecht AM. Melatonin improves cardiac and mitochondrial function during doxorubicin-induced cardiotoxicity: a possible role for peroxisome proliferator-activated receptor gamma coactivator 1-alpha and sirtuin activity? Toxicol Appl Pharmacol. 2018. https://doi.org/10.1016/j.taap.2018.06.031.

26.

Holmström KM, Kostov RV, Dinkova-Kostova AT. The multifaceted role of Nrf2 in mitochondrial function. Curr Opin Toxicol. 2016;1:80–91. https://doi.org/10.1016/j.cotox.2016.10.002.CrossRefPubMedPubMedCentral

27.

Li X, Wang H, Gao Y. Protective effects of Quercetin on mitochondrial biogenesis in experimental traumatic brain injury via the Nrf2 signaling pathway. PLoS One. 2016;11(10):e0164237. https://doi.org/10.1371/journal.pone.0164237.CrossRefPubMedPubMedCentral

Titel: Vildagliptin reduces myocardial ischemia-induced arrhythmogenesis via modulating inflammatory responses and promoting expression of genes regulating mitochondrial biogenesis in rats with type-II diabetes
verfasst von: Qin Yang
Wenwei Ai
Lei Nie
Chen Yan
Su Wu
Publikationsdatum: 18.12.2019
Verlag: Springer US
Schlagwörter: Ventricular Tachycardia
Ventricular Fibrillation
Vildagliptin
Erschienen in: Journal of Interventional Cardiac Electrophysiology / Ausgabe 3/2020
Print ISSN: 1383-875X
Elektronische ISSN: 1572-8595
DOI: https://doi.org/10.1007/s10840-019-00679-9

Neu im Fachgebiet Kardiologie

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2020

Costs and long-term outcomes following pulmonary vein isolation for atrial fibrillation in elderly patients using second-generation cryoballoon vs. open-irrigated radiofrequency in China

Acute and long-term outcomes of left-sided atrioventricular node ablation in patients with atrial fibrillation

Reduction of radiation and contrast agent exposure in a cryoballoon ablation procedure with integration of electromagnetic mapping and intracardiac echocardiography: a single center experience

One-year outcomes after pulmonary vein isolation plus posterior wall isolation and additional non-pulmonary vein trigger ablation for persistent atrial fibrillation with or without contact force sensing: a propensity score-matched comparison

Impedance drop predicts acute electrical reconnection of the pulmonary vein-left atrium after pulmonary vein isolation using short-duration high-power exposure