The atheroprotective effects of highdensity lipoprotein cholesterol

While excessive mmLDL plays an important proinflammatory role in atherosclerosis, HDL and its associated apoA-I exert a corresponding cardiovascular benefit through the RCT pathway and several other important protective mechanisms.16 HDL also has beneficial antioxidant and anti-inflammatory properties and improves endothelial dysfunction. HDL contains two antioxidant enzymes, paraoxonase and platelet-activating factor (PAF) acetylhydrolase (PAFAH), that not only inhibit the oxidation of LDL but also help degrade oxidized phospholipids within oxLDL. HDL and its associated apoA-I protect endothelial cells from damage induced by oxLDL. HDL also displays anti-inflammatory properties, since pretreatment of human endothelial cells with HDL inhibits the cytokine-induced expression of cell adhesion molecules.

Alternatively, overall HDL functionality may be more important than absolute HDLc levels, since recent data indicate that HDL has both proinflammatory and anti-inflammatory properties. HDL isolated and characterized from the plasma of a small group of CHD patients exhibited a more proinflammatory profile in vitro based on its lipid peroxide content and ability to alter LDL-induced monocyte chemotaxis than HDL obtained from age- and sex-matched controls.23 These preliminary results suggest that the proinflammatory characteristics of HDL from CHD patients may be a better predictor of overall risk than absolute HDLc levels. However, no large trials have yet been conducted to confirm this hypothesis.

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