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Jan 29, 2009
 |  BC Innovations  |  Cover Story

Wising up to NPYs

In the mid-1990s, neuropeptide Y was thought to be a promising obesity target based on its activity in the CNS as a potent feeding stimulator. However, the approach didn't succeed and only one company is still working in that space. But in a turn of events, two new studies now suggest that the peptide hormone could actually be a target in atherosclerosis and coronary artery disease.

One study, published inPublic Library of Science Genetics by a team at Duke University School of Medicine, links mutations near the gene encoding neuropeptide Y (NPY) to higher risk of early onset CAD.1

A second study, published in the Journal of Neuroscience, examined the synthesis and secretion of an NPY variant associated with atherosclerosis in Scandinavian families.2

NPY and its receptors traditionally have been studied in the CNS, where they regulate appetite, emotion and libido. However, previous rat studies did hint that NPY signaling could affect recovery from arterial injury, which can trigger CAD.3

The Duke study shores up NPY's cardiovascular function with human genomewide association data and experiments in mice linking the peptide and one of its receptors to the development of atherosclerosis.

"The strength of our study is that we combine a lot of methods to clinch the case for neuropeptide Y in coronary artery disease," said Svati Shah, assistant professor of medicine at Duke and the lead author of the study.

Risky linkage

NPY is the latest of several CAD risk genes identified by Shah's team using DNA from a panel of families with a high incidence of early-onset CAD. In an earlier study called GENECARD, the Duke team and partners at GlaxoSmithKline plc identified several chromosomal regions with markers that correlated with CAD onset at an early age.4 GSK was not involved with the new study, according to a spokesperson.

The GENECARD study was published in 2004, and the Duke team has since whittled the relatively broad disease-linked chromosomal regionsdown to candidate genes, thanks to improved marker density and statistical methods.

Shah told SciBX that the NPY locus was not the strongest of the hereditary CAD signals in the study. This is likely because only a small fraction of subjects in...

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