title: Cellular and molecular mechanisms for rapid regression of atherosclerosis: from bench top to potentially achievable clinical goal.
abstract: OBJECTIVE
  Decades of literature have unambiguously demonstrated regression and remodeling of atherosclerotic lesions, including advanced plaques. Recent insights into underlying mechanisms are reviewed.
  
  
  RESULTS
  Factors promoting regression include decreased apolipoprotein B-lipoprotein retention within the arterial wall, efflux of cholesterol and other harmful lipids from plaques, and emigration of lesional foam cells followed by entry of healthy phagocytes that remove necrotic debris and other plaque components. Cellular lipid efflux and foam cell emigration can occur surprisingly rapidly once the plaque milieu is improved. Lipid efflux and foam cell emigration each involve specific molecular mediators, many of which have been identified. Necrotic debris removal can be surprisingly comprehensive, with essentially full disappearance documented in animal models.
  
  
  CONCLUSIONS
  The essential prerequisite for regression is robust improvement in plaque milieu, meaning large plasma reductions in atherogenic apolipoprotein B-lipoproteins or brisk enhancements in 'reverse' lipid transport from plaque into liver. Importantly, the processes of regression are consistent with rapid correction of features characteristic of the rupture-prone, vulnerable plaques responsible for acute coronary syndromes. New interventions to lower apolipoprotein B-lipoprotein levels and enhance reverse lipid transport may allow regression to become a widespread clinical goal. Strategies based on recent mechanistic insights may facilitate further therapeutic progress.
authors.affiliation: Department of Medicine/Division of Endocrinology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Kevin Jon
authors.initials: KJ
authors.lastname: Williams
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Feig
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D015195:Drug Design; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008954:Models, Biological; D016896:Treatment Outcome
chemical_list: D001055:Apolipoproteins B; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL