Lipidomics Study Highlights Interaction of Aspirin with Omega-6 Fatty Acids to Lower Cholesterol Levels

A recent paper described how metabolism centered on the omega-6 polyunsaturated fatty acid arachidonic acid (AA) is linked to the way the body deals with cholesterol, which is intimately related to the risk of developing cardiovascular disease.

Investigators at Innsbruck Medical University (Austria) combined data from a genome-wide association study (GWAS) that screened more than 100,000 individuals of European ancestry with results from studies of mediator lipidomics and from functional validation studies carried out in mice.

Lipidomics, the systematic decoding of lipid-based information in biosystems, is comprised of identification and profiling of lipids and lipid-derived mediators. It is an emerging field of biomedical research that includes complex lipidome analysis. A lipidome is the comprehensive and quantitative description of a set of lipid species present in an organism. Lipidomics involves systems-level identification and quantization of thousands of pathways and networks of cellular lipids molecular species and their interactions with other lipids, proteins, and other moieties in vivo.

Results presented in a paper published in the October 16, 2014, online edition of the journal Cell Metabolism showed that the Alox5 (arachidonate 5-lipoxygenase) gene, which encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid was closely associated with plasma cholesterol and HDL (high density lipoprotein)-cholesterol. Another group of Alox5 products, the lipoxins, was found to interact with aspirin to reduce levels of circulating cholesterol by increasing expression by liver cells of the gene for the bile salt export pump Abcb11 (ATP-binding cassette, sub-family B member 11).

Abcb11 is a membrane-associated protein and is a member of the superfamily of ATP-binding cassette (ABC) transporters and a member of the MDR/TAP subfamily. This particular protein is responsible for the transport of taurocholate and other cholate conjugates from liver cells to the bile. In humans, the activity of this transporter is the major determinant of bile formation and bile flow. Induction of Abcb11 enhanced reverse cholesterol transport, one key function of HDL.

"Aspirin is known to prevent cardiovascular disease due to its anti-thrombotic and anti-inflammatory effects. We now identified a third mechanism by which aspirin may confer protection," said senior author Dr. Ivan Tancevski, an internist at Innsbruck Medical University. "Our findings could help pave the way for novel therapeutic approaches to prevent cardiovascular disease and its associated clinical sequelae, including heart attacks and stroke."

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