Hyperleptinemia Results in Systemic Inflammation and the Exacerbation of Ischemia-Reperfusion Myocardial Injury: The Involvement of the JAK/STAT Pathway

Aim: Hyperleptinemia potentiates the effects of many atherogenic factors, such as inflammation, platelet aggregation, migration, hypertrophy, proliferation of vascular smooth muscle cells, and endothelial cell dysfunction. The present study analysed the effects of long-term hyperleptinemia in an in vivo myocardial ischemia-reperfusion model to demonstrate whether the in vivo deleterious effect also affects cardiac structure and function. Main methods: Rats by were subcutaneously administered leptin for 8 days to estimate the involvement of the JAK/STAT pathway. Data from 58 male Wistar rats were included in the final analysis. Myocardial infarction (MI) was modelled by the 30-minute ligation of the main left coronary artery followed by 120-minute reperfusion. Hemodynamic measurements, electrocardiography monitoring, echocardiography, myocardial infarct size and area at risk, blood biochemical parameters, leptin, IL-6, TNF-alpha, FGF-21, and cardiomyocyte morphology were measured. Statistical analyses were performed using IBM SPSS Statistics v.26. Key findings: Eight-day hyperleptinemia in rats led to increased an blood pressure and heart rate, myocardial hypertrophy, impaired LV function, an increased frequency of ischemic arrhythmias, dyslipidaemia, systemic inflammation, and an increased size of induced myocardial infarction. Significance: The blockade of the JAK/STAT signalling pathway effectively reversed the negative effects of leptin, including increased blood pressure and total cholesterol. Funding Information: The study has been supported by the grant from the Ministry of Science and Higher Education of the Russian Federation (agreement 075-15-2020-800). Declaration of Interests: None to declare. Ethics Approval Statement: This study was conducted in conformance with the policies and procedures detailed by the “Institutional Animal Care and Use Committee” (IACUC). All animal experimental protocols and procedures were reviewed and approved by the Committee for the Control of the Maintenance and Use of Laboratory Animals of the V. A. Almazov National Medical Research Center (date: 06-FEB-2020, application number: 20-01).