MicroRNAs in circulating microvesicles and plasma as biomarkers that complement the clinical diagnosis of diabetic dyslipidemia and its complications

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research funded by grants of the Romanian Ministry of Education and Research, CNCS-UEFISCDI, project no. PN-III-P1-1.2-PCCDI-2017–0527 (Contract no. 83PCCDI/2018), project no. PN-III-P1-1.1-TE-2019–0811, within PNCDI III” (Contract no. TE 97/2020) Background Dislypidemia is a major risk factor for cardiovascular diseases as well as for diabetes where often leads to severe microvascular complications. Reportedly, microRNAs (miRNAs) associated with microvesicles (MVs) regulate cellular mechanisms in the progression of diabetic dyslipidemia. We hypothesised that detection of the changes in plasma MV components could be used as early biomarkers to prevent the irreversible effects of diabetic dyslipidemia. Purpose: of this study was to search whether in diabetic dyslipidemia with/without microvascular complications there are modifications of the circulating MVs and plasma miRNAs and whether these changes could be predictive of the disease evolution. Methods Plasma/sera was collected from diabetic patients with dyslipidemia with/without microvascular complications and the main parameters and the inflammatory markers were assessed. Results showed that, compared to either diabetes or dyslipidemia alone, in the diabetic dyslipidemic patients, significant increases in plasma glucose, cholesterol, LDL-cholesterol, triglyceride concentrations, systolic blood pressure were present. In addition, high levels of circulating IL-6 and MVs-derived from endothelial cells (CD144+), platelets (CD41+), macrophages (CD14+), and leucocytes (CD18+) were detected. Significant changes were found in plasma miRNAs and MV-associated miRNAs: 122,-132,-143,-200b,-212, decreased miR-34a,-155,-218 expressions in MVs, and reduced miR-21,-34a,-132,-143 expressions in plasma. Notably, when microvascular complications were associated to diabetic dyslipidemia, we found significant changes such as increased expression of miR-21,-34a,-122,-126,-143,-218,-223 in MV and plasma miR-143,-132 and decreased miR-200b,-212 in MVs and plasma miR-223. Conclusion In patients with diabetic dyslipidemia and, in particular, with diabetic dyslipidemia associated with microvascular complications, a significant modification in the plasma MV content and miRNAs occur suggesting that they could turn into biomarkers and potential diagnostic tool for diabetic dyslipidemia and its complications.