miRNAs are small regulatory RNA molecules the modulate gene expression by binding to their target mRNAs and either promoting mRNA degradation or inhibiting translation. miRNAs also circulate in plasma in association with exosomes. In the past year, we found that miRNAs can also associate with lipoproteins (ref. 2). Furthermore, we found that the content of miRNAs can vary with dyslipidemias, indicating that they can potentially serve as biomarkers for cardiovascular disease. Delivery of miRNAs by cellular uptake of exosomes has been shown to modulate gene expression. Using reconstituted HDL containing miRNAs, we were able to deliver miRNAs to cells via the SR-BI receptor and alter the expression of their target genes, which indicates that delivery of endogenous miRNAs by lipoproteins can potentially alter gene expression. Future studies will be aimed at understanding the role of both extracellular and intracellular miRNAs on lipid metabolism.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2011
Total Cost
$1,032,935
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Vickers, Kasey C; Shoucri, Bassem M; Levin, Michael G et al. (2013) MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia. Hepatology 57:533-42
Vickers, Kasey C; Palmisano, Brian T; Shoucri, Bassem M et al. (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423-33
Vickers, Kasey C; Remaley, Alan T (2010) MicroRNAs in atherosclerosis and lipoprotein metabolism. Curr Opin Endocrinol Diabetes Obes 17:150-5
Vickers, Kasey C; Palmisano, Brian T; Remaley, Alan T (2010) The role of noncoding ""junk DNA"" in cardiovascular disease. Clin Chem 56:1518-20