BioWorld International Correspondent
LONDON — People who regularly down a glass or two of red wine with their evening meal, and vaguely hope it might do them some good at the same time, can now congratulate themselves for almost certainly reducing their risks of coronary heart disease. Researchers in the UK have proved that an ingredient in red wine is able to reduce the production by cells of a molecule that contributes to atherosclerosis.
Roger Corder, professor of experimental therapeutics in the William Harvey Research Institute at Barts and the London, Queen Mary’s School of Medicine and Dentistry, told BioWorld International that understanding the precise mechanism by which the active ingredient in red wine has this effect may assist the development of new treatments to prevent heart disease.
He and his colleagues have published their findings in Nature in a brief communication titled “Endothelin-1 synthesis reduced by red wine.”
Corder, who himself regularly drinks red wine, said, “I guess I wanted to know, as much as many other wine drinkers do, whether there really is a health benefit and how that is exerted.”
He decided to find out whether inhibition of synthesis of a molecule called endothelin — which he has worked on for more than 10 years — could explain the health benefits of red wine. Endothelin is a peptide of 21 amino acids that is synthesised primarily in the endothelium that lines blood vessels and in vascular smooth muscle during inflammation. It causes blood vessels to constrict and stimulates proliferation of vascular smooth muscle.
Much scientific evidence now suggests that endothelin plays an important role in the development of atherosclerosis. Patients having coronary artery angioplasty who have higher plasma endothelin levels tend to have greater numbers of other sites affected by atherosclerosis. In animal studies, researchers have shown that endothelin antagonists can prevent atherosclerotic lesions from forming. In patients with coronary artery disease, endothelin antagonists can dilate the coronary vessels. Furthermore, histological studies show that endothelin is synthesized around atherosclerotic lesions and within them, but not by other cells close by.
“All this seems to me to be strong evidence that an antiendothelin treatment could reduce the incidence of coronary artery disease,” Corder said.
But could red wine act as such a treatment? Corder designed some experiments to find out. He and his colleagues first showed that polyphenols in red wine made from Cabernet Sauvignon grapes were able to reduce levels of synthesis of endothelin-1 by endothelial cells taken from bovine aorta. Transcription of the human gene encoding endothelin-1 was suppressed in studies using a reporter gene assay.
Next, Corder and his colleagues prepared alcohol-free extracts from 23 red wines, four white wines, one ros wine and one red-grape juice, which they added to similar cell cultures. They found that the white wines and the ros wine had no effect on endothelin synthesis. The red-grape juice had some effect — but the red wines were most potent of all. Among these, those wines with the highest levels of polyphenols were most effective at inhibiting endothelin synthesis.
“This finding was initially very exciting, and the more we did it, the more reproducible it was. We were also excited to realize that there was a huge variation between the best and worst wines, in terms of their ability to inhibit endothelin production. We also felt excited by the fact that vin de table was as good as chateau wines,” Corder said. “This implies a mechanism for the French paradox — the observation that deaths from coronary artery disease are much lower in France than in the UK, even though both countries’ populations consume similar levels of saturated fats — because, in general, people in France drink basic wine of a medium-to-low quality, not chateau wines.”
Experiments carried out by the group showed that an extract of red wine modified tyrosine-kinase signaling in endothelial cells. Corder and his group want to find out what component of the extract has this effect, and which particular kinase it interferes with.
“We also want to compare the effect of consuming wine on an empty stomach with that of consumption with food since frequently the French consume their wine with meals,” he said. “From the activity we showed, if we only have 10 percent absorption of the active ingredient, you would probably need two glasses of wine a day, but if we have 50 percent absorption, you may only need half a glass of the best wine a day to have a protective effective.”
Within the next few months, Corder hopes to have purified fractions of the active ingredient that will allow him and his colleagues to determine its structure.