Saturday, January 29, 2011

Notch up a victory for alcohol and heart health

OK, we all know that wine is good for the heart; French paradox, old news. And if you are at all interested in anti-aging, you will have heard that wine’s benefits are attributed to the polyphenol antioxidants from the skins, including resveratrol, quercetin, and a menagerie of other exotic molecules. But the role of alcohol has long been questioned. Even though the epidemiologic evidence points to a contributory part for alcohol, the exact mechanisms by which it might accomplish this have not been well understood, other than favorably shifting the high density/low density cholesterol ratio. New findings implicate a signaling molecule called Notch, another one of those exotic breeds that seem to be involved in a lot of things once we get to know them.

     Vessel thickening is reduced in the carotid arteries of mice fed the equivalent of two drinks, compared to no-alcohol controls. (Credit: Image courtesy of University of Rochester Medical Center)



Notch does seem to be a multitasker. One important position it occupies is signaling immune system cells called helper T-cells to differentiate into specific subtypes. Research on notch may lead to new therapies for a range of immune system diseases and certain types of infection that require targeted immune responses. But notch, a receptor protein in cell walls, influences many types of cells on their differentiation pathways. This potentially involves notch in several types of cancer too, and the inflammatory processes that lead to the formation of plaques in the walls of arteries. This is where alcohol comes into the picture.

Atherosclerosis is not a passive buildup of sludge in the arteries, but a dynamic condition that includes thickening and proliferation of the muscle cells in the artery wall (it is relaxation or contraction of these muscles that sets blood pressure.) The more thickening that occurs, the stiffer the artery and the more likelihood of a clot and a heart attack. These specialized muscle cells are triggered to grow by notch signaling, a process inhibited by alcohol.

It’s probably fair to say that recognizing the undercurrent of chronic inflammation as one of the most important causes of cardiovascular disease was a major breakthrough. Your aspirin a day is effective not because it protects against a clot forming but because of its anti-inflammatory actions. Now we know that inhibition of notch may be another important pathway for reducing heart disease risk, at least according to a paper from the University of Rochester Medical School. Using muscle cell cultures from human arteries and intact arteries from mice, the researchers identified notch as a sort of relay signal for the cells to divide and grow. Alcohol was identified as a notch inhibitor, and therefore in the right amounts a positive factor in helping to maintain supple arteries. I say cheers to that.

Morrow D, Cullen JP, Liu W, Cahill PA, Redmond EM. Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway. Arterio Scler Thromb Vasc Biol 2010 Dec; 30(12):2597-603.

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