Extracellular microRNAs (miRNA) are transported between organs in plasma by protective carriers, including high-density-lipoproteins (HDL). Cardiovascular disease (CVD) represents a significant health and financial burden to our society; however, miRNAs are a new class of drug targets that may be used to treat atherosclerosis. Our published reports and preliminary data suggest that HDL-miRNAs likely serve as biological hormones that regulate systemic homeostasis and have potential to be controlled to treat or prevent CVD. Atherosclerosis is a complex pathophysiology mediated by extensive cell-to-cell communication and gene regulation. The main objectives of this study are to define novel HDL-miRNA intercellular communication mechanisms and the physiological impact of HDL-miRNA communication in CVD. To complete these goals we will, i.) Map the distribution of HDL-miRNA communication and gene regulation, ii.) Identify novel HDL-miRNA target genes associated with inflammation and metabolism, iii.) Determine the role HDL-miR-223 plays in atherosclerosis, and iv.) Control HDL-miRNA communication to treat metabolic dysregulation and atherosclerosis. Collectively, this study will provide remarkable and fundamental insight into HDL biology, and defines the functional relevance and consequences of HDL-miRNA communication in health and disease in animals and humans. As constructed, these studies will take advantage of current concepts in lipoprotein biology and use state-of-the art methods and equipment, including extensive use of high-throughput sequencing.
High-Density Lipoproteins (HDL) transport microRNAs (miRNA) between organs in an endocrine-like communication pathway. Strikingly, HDL-miRNAs are significantly altered in hypercholesterolemia and atherosclerosis in both humans and mice. Currently, it is unknown if changes to HDL-miRNAs promote or antagonize atherosclerosis; however, these projects aim to study key mechanisms of this pathway and define the cells and outcomes of cardiovascular communication in the HDL network.
Showing the most recent 10 out of 21 publications
