TY - JOUR
T1 - Rapid regression of atherosclerosis
T2 - Insights from the clinical and experimental literature
AU - Williams, Kevin Jon
AU - Feig, Jonathan E.
AU - Fisher, Edward A.
PY - 2008/2
Y1 - 2008/2
N2 - Looking back at animal and clinical studies published since the 1920s, the notion of rapid regression and stabilization of atherosclerosis in humans has evolved from a fanciful goal to one that might be achievable pharmacologically, even for advanced plaques. Our review of this literature indicates that successful regression of atherosclerosis generally requires robust measures to improve plasma lipoprotein profiles. Examples of such measures include extensive lowering of plasma concentrations of atherogenic apolipoprotein B (apoB)-lipoproteins and enhancement of 'reverse' lipid transport from atheromata into the liver, either alone or in combination. Possible mechanisms responsible for lesion shrinkage include decreased retention of apoB-lipoproteins within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris and other components of the plaque. Unfortunately, the clinical agents currently available cause less dramatic changes in plasma lipoprotein levels, and, thereby, fail to stop most cardiovascular events. Hence, there is a clear need for testing of new agents expected to facilitate atherosclerosis regression. Additional mechanistic insights will allow further progress.
AB - Looking back at animal and clinical studies published since the 1920s, the notion of rapid regression and stabilization of atherosclerosis in humans has evolved from a fanciful goal to one that might be achievable pharmacologically, even for advanced plaques. Our review of this literature indicates that successful regression of atherosclerosis generally requires robust measures to improve plasma lipoprotein profiles. Examples of such measures include extensive lowering of plasma concentrations of atherogenic apolipoprotein B (apoB)-lipoproteins and enhancement of 'reverse' lipid transport from atheromata into the liver, either alone or in combination. Possible mechanisms responsible for lesion shrinkage include decreased retention of apoB-lipoproteins within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris and other components of the plaque. Unfortunately, the clinical agents currently available cause less dramatic changes in plasma lipoprotein levels, and, thereby, fail to stop most cardiovascular events. Hence, there is a clear need for testing of new agents expected to facilitate atherosclerosis regression. Additional mechanistic insights will allow further progress.
UR - http://www.scopus.com/inward/record.url?scp=38649110177&partnerID=8YFLogxK
U2 - 10.1038/ncpcardio1086
DO - 10.1038/ncpcardio1086
M3 - Review article
C2 - 18223541
AN - SCOPUS:38649110177
SN - 1743-4297
VL - 5
SP - 91
EP - 102
JO - Nature Clinical Practice Cardiovascular Medicine
JF - Nature Clinical Practice Cardiovascular Medicine
IS - 2
ER -