February 7, 2023

A new view of a cholesterol carrier

Vanderbilt researchers developed a novel method to measure small RNAs carried by HDL and demonstrated that these molecules circulate in greater concentrations than previously believed and are likely to contribute to communication between immune cells.

High density lipoprotein (HDL) is often referred to as “good cholesterol.” However, cholesterol is just one of many types of cargo HDL can carry. In addition to shuttling cholesterol from blood to the liver, high-density lipoprotein (HDL) can also transport proteins, metabolites and small RNAs (sRNA).

The discovery of HDL’s multifaceted functions has driven researchers to focus on HDL quality versus quantity. Unfortunately, studying sRNAs carried by HDL has proven difficult due to sample loss during RNA isolation.

To avoid this, Kasey Vickers, PhD, Mark Castleberry, PhD, and colleagues developed a novel method of measuring HDL sRNAs using a lipid-penetrating RNA-specific fluorescent dye that allows them to quantify lipoprotein RNA without performing RNA isolations. This method enabled them to measure and trace HDL’s sRNA transport between different immune cells and investigate related cellular mechanisms.

The researchers determined that HDL accepts sRNAs from dendritic cells (immune cells responsible for initiating antigen-specific responses) and transfers them to macrophages, potentially through HDL retro-endocytosis.

The article, published in the Journal of Lipid Research, suggests that lipoprotein-shuttled sRNAs circulate in greater concentrations than previously recognized and likely contribute to communication between immune cells.

Co-authors included researchers at four Japanese universities and, from Vanderbilt University Medical Center, Chase Raby, Anca Ifrim, RN, MacRae Linton, MD, and Danielle Michell, PhD. 

This work was supported in part by the Ministry of Education, Culture, Science and Technology of Japan, a W.M. Keck Foundation Medical Research Award, and National Institutes of Health grant HL116263.