Coronary artery disease (CAD) ranks as the leading cause of death in the Western world. The most widely used therapeutics utilized for the treatment of CAD are the lipid-lowering drugs, which lower plasma cholesterol. However lowering cholesterol alone may not be sufficient to provide benefit to all patient populations at risk for CAD. This creates an unmet medical need. Emerging knowledge of the genesis, progression and regression of atherosclerosis, that leads to CAD permits evaluation of other therapeutic strategies. This review will evaluate two such naturally occurring paradigms, the nitric oxide pathway and the high-density lipoprotein system which are nature's defense mechanisms against atherosclerosis and may lead to next generation therapeutics against CAD.
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