Effects of HDL-associated miRNAs on HDL functionality

Abstract

It is generally accepted that high-density lipoprotein (HDL) exerts atheroprotective functions, such as promoting cholesterol efflux from macrophages and modulating inflammation. However, in several diseases, such as chronic kidney disease (CKD), HDL functionality is compromised and the cause for this dysfunction has not yet been fully clarified. Recently, it has been shown that HDL transports and delivers functional miRNAs to recipient cells and that the levels of these HDL-associated miRNAs are altered in several diseases. Therefore, we hypothesized that CKD patients have an altered profile of HDL-associated miRNAs and that these miRNAs are partially responsible for HDL functions, i.e. modulating inflammation. MiRNA levels (miR-223, miR92a, miR-135a, miR-33a) were quantified in apoB-depleted serum from CKD patients and hypertensive, non-CKD controls using RT-qPCR. The inflammatory responses of J774 macrophages and endothelial cells (HMEC) were determined by quantification of cytokine production (TNF' and IL-10) using ELISA and by gene expression analysis of chemotactic (CCL2) as well as adhesion molecules (ICAM-1 and VCAM-1), respectively. The HDL-associated miRNA profile was altered in CKD patients compared to the hypertensive controls. MiR-223 showed a marked decrease with progression of the disease. Furthermore, HDL was able to deliver different miRNAs to macrophages and endothelial cells after enrichment, where some miRNAs then affected the inflammatory response.