Dysfunctional HDL as a diagnostic and therapeutic target

The atheroprotective effects of HDL are mediated by several mechanisms including its role in reverse cholesterol transport and via its anti-inflammatory properties. However, not all HDL is functionally similar. HDL and apolipoprotein A-I may become dysfunctional or even pro-inflammatory, and thus promote atherosclerosis. ApoAI post-translational modification can have a large impact on its function. Myeloperoxidase modification of apoAI impairs it function as a cholesterol acceptor, and the molecular changes induced by myeloperoxidase have been studied in detail. These studies provide the basis for the development of an oxidant resistant form of apoAI and clinical measures of HDL modification and dysfunction, which may be useful as a treatment criterion. Keywords HDL; apolipoprotein A-I; reverse cholesterol transport; myeloperoxidase; anti-inflammatory HDL-cholesterol (HDL-C) is an independent protective factor for coronary artery disease (CAD), as demonstrated by numerous epidemiological studies, such as the Framingham Heart Study1. In interventional settings, niacin, which effectively raises HDL levels, given as a monotherapy or combined with other drugs has been shown to reduce CAD an