PPAR agonists as direct modulators of the vessel wall in cardiovascular disease

Successful management of cardiovascular (CV) disease and associated metabolic syndromes, such as diabetes, is a major challenge to the clinician. Reducing CV risk factors, such as abnormal lipid profiles, insulin resistance or hypertension is the foundation of such therapy. A relatively new class of therapeutic agent, activators of peroxisome proliferator-activated receptors (PPAR), is poised to make a major impact with regard to several areas of risk factor management. However, there is growing evidence that PPAR agonists may also influence the CV system directly by modulating vessel wall function. These observations suggest that additional benefit, in the treatment of CV disease, may derive not only from the ability of agents to modify risk factors but also to influence directly the cellular mechanisms of disease within the vessel wall. A precedent for this dual action comes from examination of the effects of inhibitors of HMG CoA reductase (statins), where risk factor modulation is accompanied by direct actions on the vessel wall. In this review, we summarize the evidence suggesting that PPAR agonists may directly modulate vessel wall function, and that these may parallel those effects reported recently for the statins.