title: Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice.
abstract: OBJECTIVE
  The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease.
  
  
  BACKGROUND
  Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E(-/-) (ApoE(-/-)) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection.
  
  
  METHODS
  Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE(-/-) mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27.
  
  
  RESULTS
  Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551-5,475] vs. 6,200 pg/ml [2,575-9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability.
  
  
  CONCLUSIONS
  In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Tara A
authors.initials: TA
authors.lastname: Seibert
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hibbert
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.forename: Katey
authors.initials: K
authors.lastname: Rayner
authors.forename: Trevor
authors.initials: T
authors.lastname: Simard
authors.forename: Tieqiang
authors.initials: T
authors.lastname: Hu
authors.forename: Charles M
authors.initials: CM
authors.lastname: Cuerrier
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhao
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Belleroche
authors.forename: Benjamin J W
authors.initials: BJ
authors.lastname: Chow
authors.forename: Steven
authors.initials: S
authors.lastname: Hawken
authors.forename: Kumanan R
authors.initials: KR
authors.lastname: Wilson
authors.forename: Edward R
authors.initials: ER
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D015331:Cohort Studies; D017023:Coronary Angiography / Q000379:methods; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000097:blood / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D061330:Multidetector Computed Tomography / Q000379:methods; D017063:Outcome Assessment, Health Care; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D055551:HSP27 Heat-Shock Proteins
keywords: ApoE; CAD; HFD; HSP27; IL; IQR; MACE; PBS; apolipoprotein E; atherosclerosis; coronary artery disease; coronary disease; heat shock protein; heat shock protein 27; high-fat diet; interleukin; interquartile range; major adverse cardiovascular event(s); phosphate-buffered saline