title: The effect of statins on high-risk atherosclerotic plaque associated with low endothelial shear stress.
abstract: OBJECTIVE
  Low endothelial shear stress (ESS) plays an important role in the progression and severity of atherosclerotic lesions. As 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to stabilize plaque, it would be valuable to understand how statins affect the nature of lesions in the proatherogenic and proinflammatory environment of low ESS and the effect of statins on that atherosclerotic process. The purpose of this review is to summarize the relationship among low ESS, high-risk plaque and statins.
  
  
  RESULTS
  Low ESS is a critically important determinant of plaque development and progression to high-risk plaques with large necrotic lipid core, intensive inflammation and thin fibrous cap. In addition to the proatherogenic phenotypic switching in areas of low ESS, local LDL cholesterol concentrations are also increased in areas of low ESS, which exacerbates the local atherogenic process. In experimental models, statins appear to reduce the inflammation in lesions associated with low ESS and reduce the atherosclerotic phenotype even in these high-risk prone vascular areas.
  
  
  CONCLUSIONS
  The relationship between low ESS and statins has not been fully investigated, but the available data underscore the vasculoprotective effect of statins. Understanding the mechanisms whereby statins reduce the atherogenic and inflammatory phenotype resulting from a low ESS environment would provide new insights to design strategies to prevent regional formation of high-risk, inflamed plaques likely to rupture and cause an adverse clinical event.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Saeko
authors.initials: S
authors.lastname: Takahashi
authors.forename: Michail I
authors.initials: MI
authors.lastname: Papafaklis
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Antonios P
authors.initials: AP
authors.lastname: Antoniadis
authors.forename: Ahmet U
authors.initials: AU
authors.lastname: Coskun
authors.forename: Charles L
authors.initials: CL
authors.lastname: Feldman
authors.forename: Peter H
authors.initials: PH
authors.lastname: Stone
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D013314:Stress, Mechanical
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors