Effects of rosuvastatin and metformin on resistin levels in subcutaneous, epicardial and perivascular adipose tissues of patients with ischemic heart disease
Authors: Dyleva Y , Gruzdeva O V , Belik E V , Sinitsky M Y U , Borodkina D A , Ivanov S V , Barbarash O L 
Published: October 2021

Abstract

The aim of the study was to assess the level of resistin in local fat depots and the possibility of correcting the level of resistin using rosuvastatin and metformin.

Methods
This study was performed at the Federal State Budgetary Institution's Research Institute for Complex Issues of Cardiovascular Diseases. The study included 84 patients with ischemic heart disease (IHD), who were planned to undergo coronary artery bypass grafting (CABG). The average age of the patients was 63.8 (50.1; 68.6) years. Patients were included in the study after they provided written informed consent. In order to study the combined effect of atorvastatin and metformin on the functional activity of adipocytes in the SAT, EAT, and PVAT, isolated adipocytes were cultured for 24 hours with the addition of drugs at different concentrations: 1 μmol/L atorvastatin (SigmaAldrich, China) + 1 mmol/L metformin (USP, Norway); 5 μmol/L atorvastatin + 10 mmol/L metformin. Then, the expression of mRNA resistin genes (RSTN) was assessed. Statistical analysis was performed using GraphPad Prism 6 (GraphPad Software), nonparametric tests, and multivariate statistics methods.

Results
The level of RSTN expression in the EAT was the highest compared to the SAT (2.6 times, p=0.0014) and the PVAT (1.9 times, p=0.0017). The level of secretion of the resistin in the culture medium of adipocytes corresponded to the expression of the resistin gene. Cultivation of adipocytes with rosuvastatin showed that low concentrations (1 μmol/L) did not have a significant effect on the functional activity of adipocytes. At the same time, 5 μmol/L rosuvastatin reduced the level of RSTN expression and protein secretion, but only in subcutaneous adipocytes in compared with control.
Culturing adipocytes with metformin at a concentration of 10 mmol/L reduced the level of RSTN expression and protein secretion in the culture medium in all three adipose tissues. At the same time, 1 mmol/L metformin did not have a significant effect. The use of a combination of the drugs rosuvastatin and metformin at various concentrations led to a decrease in the RSTN expression in the SAT, EAT, and PVAT, but only when 5 μmol/L rosuvastatin + 10 mmol/L metformin were used.

Conclusion
Thus, the level of resistin in adipocytes of adipose tissue of patients with IHD is influenced only by rosuvastatin at a concentration of 5 μmol/L and only on adipocytes of adipose tissue, reducing the level of RSTN expression and protein secretion in the culture medium. Metformin was more effective than rosuvastatin and at high concentrations (10 mmol/L) reduced RSTN expression and protein secretion in the culture medium regardless of the localization of adipocytes. The combined use of high concentrations of rosuvastatin (5 μmol/L) and metformin (10 mmol/L) of patients with IHD had a comparable effect with metformin at a concentration of 10 mmol/L.

Funding Acknowledgement
Type of funding sources: None.