Hyperglycemia Determines Increased Specific MicroRNAs Levels in Sera and HDL of Acute Coronary Syndrome Patients and Stimulates MicroRNAs Production in Human Macrophages

Abstract

We aimed to determine the levels of microRNAs (miRNAs) in sera and HDL of acute coronary syndrome (ACS) compared to stable angina (SA) patients with/without hyperglycemia, and evaluate comparatively the functional effect of these sera on the processing machinery proteins (Drosha, DGCR8, Dicer) and miRNAs production in human macrophages. MiRNAs levels in sera and HDL from 35 SA and 72 ACS patients and 30 healthy subjects were measured by using microRNA TaqMan assays. MiR-223, miR-92a, miR-486, miR-122, miR-125a and miR-146a levels were higher in the hyperglycemic ACS compared to normoglycemic sera. MiR-223 and miR-486 prevailed in HDL2, while miR-92a predominated in HDL3, all three miRNAs discriminating between ACS and SA patients; their levels were increased in HDL from hyperglycemic ACS patients versus normoglycemic ones. The incubation of human macrophages with sera from ACS and SA patients showed that all patients’ sera induced an increase of Drosha, DGCR8 and Dicer expressions and of selected miRNAs levels compared to control sera, the effect being higher in the case of hyperglycemic versus normoglycemic ACS sera. The addition of glucose to SA and ACS sera increased Drosha, DGCR8 and Dicer expression and miRNAs levels in the exposed macrophages. In conclusion, hyperglycemia is associated with increased miR-223, miR-92a, miR-486 levels in HDL, which discriminate between ACS and SA patients. Exposure of human macrophages to ACS compared to SA sera determines the upregulation of Drosha, DGCR8 and Dicer expression and the increase of selected miRNAs production, the effect being augmented by an increased glucose concentration.

Advances, challenges, and opportunities in extracellular RNA biology: insights from the NIH exRNA Strategic Workshop

“…Monocytes and macrophages export specific miRNAs, including miR-223-3p, to HDL (52), which can be transferred to endothelial cells and exert an antiinflammatory effect on these cells (57). HDL miRNAs have been shown to be altered in CVD and diabetes (52,53,58,59). These findings support the functional importance of the LPP exRNA transport pathway and reveal the potential of HDL-associated miRNAs as biomarkers for cardiometabolic diseases.…”

Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1 Diabetes

“…The mechanisms of increasing or decreasing circulating miRNA levels in the hyperglycemic state are still unknown. Simionescu et al (46) reported that hyperglycemia increased the levels of Drosha, DGCR8, and Dicer expression and several miRNAs (miR-223, miR-92a, miR-486, miR-122, miR-125a, and miR-146a) in human macrophages. Nishikawa et al (47) reported that hyperglycemia causes pathological changes in small vessels and results in tissue damage in endothelial cells.…”

Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach

“…Diabetes is a systemic metabolic condition, and the animal model of STZ-induced diabetes is characterized by disruption of pancreatic beta-cells, which cannot release insulin, leading to hyperglycaemia (Szkudelski, 2001). The overlap between serum and retinal expression of the focused set of dysregulated miRNAs in STZ diabetic mice would suggest that hyperglycaemia modifies miRNA expression at a systemic level (Ocłoń, Latacz, Zubel-Łojek, & Pierzchala-Koziec, 2016;Silambarasan et al, 2016;Simionescu et al, 2016). Moreover, circulating miRNAs could come from exosomes, released from several tissues, working as paracrine signalling molecules in hyperglycaemic conditions (Guay & Regazzi, 2013;Gupta, Bang, & Thum, 2010;Hashimoto & Tanaka, 2017).…”