An international team of researchers has developed a new way of visualizing the distribution of cholesterol in cells and tissues. Their studies, which provide unique insights into the movement of cholesterol into and out of cells, could eventually lead to new therapies for cardiovascular disease.
Researchers at The University of Western Australia (UWA) and the University of California, Los Angeles (UCLA) collaborated in using a new high-resolution imaging mass spectrometry approach, called NanoSIMS imaging, to visualize and quantify a specialized pool of cholesterol (“accessible cholesterol”) on the surface of cells.
Cholesterol is an essential lipid and is critical for maintaining the integrity of the plasma membrane in every cell in the body. Cholesterol and cholesterol esters are also present in lipid-rich particles in the bloodstream (called lipoproteins). Elevated levels of cholesterol in the blood are a major risk factor for coronary artery disease.
The accessible pool of cholesterol on the plasma membrane is thought to play a role in regulating production of cholesterol by cells, and it likely plays an important role in the ability of cells to unload surplus cholesterol. “Accessible cholesterol” on the surface of cells can be detected with a cholesterol-binding protein.
By taking advantage of that protein, along with NanoSIMS imaging, the UWA and UCLA team showed that the accessible pool of cholesterol is not evenly distributed on cell plasma membrane, but instead is highly enriched on specialized projections from the plasma membrane (microvilli). In the past, other scientists had speculated that microvilli play a role in moving cholesterol into and out of cells. The discovery that “accessible cholesterol” is highly enriched in microvilli lends support to that idea.
One of the leaders in the current study, Dr Haibo Jiang from the UWA Centre for Microscopy, Characterisation and Analysis, commented, “NanoSIMS imaging provides unique insights into cholesterol distribution on the plasma membrane; and future studies will make it possible to assess mechanisms by which cells dispose of excess cholesterol.”
“We would like to gain a better understanding of the mechanisms of cholesterol movement in cells and tissues,” Dr Jiang said. He added, “We believe that NanoSIMS imaging could yield new strategies for lowering cholesterol levels in the blood or at least new strategies for optimizing the effects of existing cholesterol-lowering drugs.” Dr. Jiang worked closely with a team at UCLA involving Drs. Cuiwen He, Stephen Young, Loren Fong, and Mr. Xuchen Hu. The joint UWA/UCLA paper has been published in the journal, Proceedings of the National Academy of Sciences USA (PNAS). The paper can now be viewed on the PNAS website.
Dr. Young commented that this international collaboration has a wonderful future. The team has already defined unique mechanisms for cholesterol movement in specialized cell types. He said, “The plan now is to use NanoSIMS, along with novel biochemical approaches, to investigate cholesterol distribution and cholesterol movement in multiple cell types.”
This project is supported by grants from National Heart, Lung, and Blood Institute, AMMRF and UWA Research Collaboration Awards.
David Stacey (UWA Media and Public Relations Manager) (+61 8) 6488 3229/ (+61 4) 32 637 716
Dr Haibo Jiang (Centre for Microscopy, Characterisation and Analysis) (+61 8) 6488 8068