Based on studies that date back to the 1920s, regression and stabilization of atherosclerosis in humans has gone from just a dream to one that is achievable. Review of the literature indicates that the successful attempts at regression generally applied robust measures to improve plasma lipoprotein profiles. Examples include extensive lowering of plasma concentrations of atherogenic apolipoprotein B and enhancement of reverse cholesterol transport from atheromata to the liver.
Possible mechanisms responsible for lesion shrinkage include decreased retention of atherogenic apolipoprotein B within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of lesional foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris as well as other components of the plaque. This review will highlight the role key players such as LXR, HDL and CCR7 have in mediating regression.
Although much progress has been made, there are many unanswered questions. There is, therefore, a clear need for preclinical and clinical testing of new agents expected to facilitate atherosclerosis regression with the hope that additional mechanistic insights will allow further progress.