Researchers lead by Mark Brown of Wake Forest University School of Medicine, have come up with an interesting finding that is "there is more than one way to get rid of that cholesterol, which can otherwise lead to atherosclerosis and heart disease".
A model of cholesterol loss first proposed way back in the 1920s suggested the existence of a route that didn't rely on bile. And indeed, studies in dogs unable to get cholesterol into bile showed that the animals actually experienced an increase in cholesterol loss. More recent studies in mice showed a similar thing. Even so, the researchers said that an alternative pathway has largely been ignored. As a result, scientists have made very little progress in defining the molecular pathways and players involved.
Now, Brown and his colleagues offer new evidence that helps support and clarify this alternate path for cholesterol. Researchers report that mice made unable to secrete cholesterol into bile through genetic manipulation or surgery still lose cholesterol through the feces at a normal rate. Macrophages in those animals also continued to take up cholesterol from blood vessels. The researchers believe that alternate path delivers cholesterol from the liver to the intestine directly through the bloodstream.
"The classic view of reverse cholesterol transport involved the delivery of peripheral cholesterol via HDL to the liver for secretion into bile," the researchers wrote. "In parallel, we believe that the liver also plays a gatekeeper role for nonbiliary fecal sterol loss by repackaging peripheral cholesterol into nascent plasma lipoproteins that are destined for subsequent intestinal delivery."
For the purposes of cholesterol-lowering drug discovery, it may prove fruitful to consider those two pathways as "separate and compel", claims the lead researcher.
Researchers claims that the drugs aimed to increase cholesterol loss without relying on bile will have fewer side effects (an excess of cholesterol in bile can lead to gallstones). Let us be optimistic and hope for the best, in the near future...
Ref : http://www.cell.com/cell-metabolism/abstract/S1550-4131%2810%2900186-5
