Chronic Endothelial Injury Hypothesis - Implications For The Treatment and Prevention of Arteriosclerosis

Implications For The Treatment and Prevention of Arteriosclerosis

The role LDL plays suggests two different approaches to treatment and prevention. The first approach involves discouraging the accumulation of LDL by lowering the levels of serum LDL, an idea more closely associated with the lipid hypothesis. A major breakthrough involved the discovery of statins, a class of drugs which help to clear LDL from the bloodstream. It has been demonstrated conclusively that elevated levels of LDL are associated with higher risk of mortality from coronary heart disease (CHD); it has also been shown that statins substantially lower the risk of mortality in patients with high LDL.

A second approach would be to discourage the oxidation of LDL, thereby breaking the inflammatory cycle. Lipoproteins consist of a packaging of triglycerides and esterfied cholesterol within a monolayer shell consisting of phospholipids and a class of proteins called apolipoproteins. The phospholipds are amphipathic, consisting of a hydrophobic tail which faces inwards, binding with the triglycerides and cholesterol, and a hydrophilic head which faces outwards, making the lipoproteins water soluble.

Polyunsaturated fatty acids (PUFA) contained in the outer shell make the lipoproteins especially susceptible to oxidation. However, lipoproteins also contain antioxidants which protect the components, vitamin E and carotenoids being the two major naturally-occurring antioxidants in human lipoprotein.

Although some studies have shown positive results following anti-oxidant therapy with vitamin C, vitamin E therapy has attracted the most public attention. There have been some positive results, though recent studies have shown no benefit for antioxidant therapy on mortality among patients at risk for CHD.,