Quick, what biomarker whose nameÂ starts with â€œcho-” is connected with cardiovascular disease? Very understandable if your first thought is â€œcholesterol.â€ Today Iâ€™d like to shift focus to a molecule with a similar name, but a very different structure: choline.
Choline, a common dietary lipid component and an essential nutrient, came to prominence in cardiology research in 2011 when researchers at the Cleveland Clinic found that choline and its relatives can contribute to cardiovascular disease in a way that depends upon intestinal bacteria. In the body, choline is part of two phospholipids that areÂ abundant in cell membranes, and is also a precursor for the neurotransmitter acetylcholine. SomeÂ bacteria can turn choline (and also carnitine) into trimethylamine N-oxide (TMAO), high levels of which predict cardiovascular disease in humans. TMAO in turn seems to alter how inflammatory cells take up cholesterol and lipids.
Researchers at Emory arrived at choline metabolites and their connection to atherosclerosis by another route. Hanjoong Jo and his colleagues have been productively probing the mechanisms of atherosclerosis with an animal model. Very briefly: inducing disturbed blood flow in mice, in combination with a high fat diet, can result in atherosclerotic plaque formation within a few weeks. Joâ€™s team has used this model to examine changes in gene activation, microRNAs, DNA methylation, and now, metabolic markers.
Talking about this study at Emoryâ€™s Clinical Cardiovascular seminar on Friday, metabolomics specialist Dean Jones said he was surprised by the results, which were recently published by the American Journal of Physiology (to be precise, their â€˜omics journal). The lead author is instructor Young-Mi Go.
â€œI would not have guessed that local alterations in blood flow would lead to systemic changes in metabolism,â€ Jones said. â€œThe most fascinating part is that disturbed flow generates changes that have a similar metabolic character to those identified by Hazen and his colleagues.â€
The Emory team showed that disturbed blood flow leads to increased levels of choline and betaine but decreased levels of phosphatidylcholine, which could be a result of cellular defenses against inflammatory signaling. Disturbed flow also leads to changes in amino acid metabolism.
Jones said these findings were an example of the mechanistic insights that could be achieved by metabolomics studies; a related human metabolomics study of cardiovascular disease at Emory is starting to generate intriguing data, he said.
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