Does reversal of oxidative stress and inflammation provide vascular protection?

Chronic inflammation is a pathogenic feature of atherosclerosis and cardiovascular disease mediated by substances including angiotensin II, proinflammatory cytokines, and free fatty acids. This promotes generation of reactive oxygen species in vascular endothelial cells and smooth muscle cells, which mediate injury through several mechanisms. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidaemia and the renin-angiotensin-aldosterone system (RAAS) at multiple levels contribute importantly to a variety of risk factors. Therefore, combination therapy that simultaneously addresses multiple mechanisms for the pathogenesis of atherosclerosis is an attractive emerging concept for slowing progression of atherosclerosis. Combined therapy with statins, peroxisome proliferator-activated receptors, and RAAS blockade demonstrates additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors due to both distinct and interrelated mechanisms. These additive beneficial effects of combined therapies are consistent with laboratory and recent clinical studies. Thus, combination therapy may be an important paradigm for treating and slowing progression of atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance.