title: Epicatechin attenuates atherosclerosis and exerts anti-inflammatory effects on diet-induced human-CRP and NFκB in vivo.
abstract: OBJECTIVE
  Previous studies investigating flavanol-rich foods provide indications for potential cardioprotective effects of these foods, but the effects of individual flavanols remain unclear. We investigated whether the flavanol epicatechin can reduce diet-induced atherosclerosis, with particular emphasis on the cardiovascular risk factors dyslipidaemia and inflammation.
  
  
  METHODS
  ApoE*3-Leiden mice were fed a cholesterol-containing atherogenic diet with or without epicatechin (0.1% w/w) to study effects on early- and late-stage atherosclerosis (8 w and 20 w). In vivo effects of epicatechin on diet-induced inflammation were studied in human-CRP transgenic mice and NFκB-luciferase reporter mice.
  
  
  RESULTS
  Epicatechin attenuated atherosclerotic lesion area in ApoE*3-Leiden mice by 27%, without affecting plasma lipids. This anti-atherogenic effect of epicatechin was specific to the severe lesion types, with no effect on mild lesions. Epicatechin mitigated diet-induced increases in plasma SAA (in ApoE*3-Leiden mice) and plasma human-CRP (in human-CRP transgenic mice). Microarray analysis of aortic gene expression revealed an attenuating effect of epicatechin on several diet-induced pro-atherogenic inflammatory processes in the aorta (e.g. chemotaxis of cells, matrix remodelling), regulated by NFκB. These findings were confirmed immunohistochemically by reduced lesional neutrophil content in HCE, and by inhibition of diet-induced NFκB activity in epicatechin-treated NFκB-luciferase reporter mice.
  
  
  CONCLUSIONS
  Epicatechin attenuates development of atherosclerosis and impairs lesion progression from mild to severe lesions in absence of an effect on dyslipidaemia. The observed reduction of circulating inflammatory risk factors by epicatechin (e.g. SAA, human-CRP), as well as its local anti-inflammatory activity in the vessel wall, provide a rationale for epicatechin's anti-atherogenic effects.
authors: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK Leiden, The Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands; Top Institute Food and Nutrition, Nieuwe Kanaal 9A, 6709 PA Wageningen, The Netherlands. Electronic address: martine.morrison@tno.nl.
authors: Martine
authors: M
authors: Morrison
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands; Top Institute Food and Nutrition, Nieuwe Kanaal 9A, 6709 PA Wageningen, The Netherlands.
authors: Roel
authors: R
authors: van der Heijden
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1 (EA11), 9713 GZ Groningen, The Netherlands.
authors: Peter
authors: P
authors: Heeringa
authors: Molecular Endocrinology and Molecular Imaging, Department of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors: Eric
authors: E
authors: Kaijzel
authors: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK Leiden, The Netherlands.
authors: Lars
authors: L
authors: Verschuren
authors: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Sognsvannsveien 9, 0372 Oslo, Norway.
authors: Rune
authors: R
authors: Blomhoff
authors: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK Leiden, The Netherlands.
authors: Teake
authors: T
authors: Kooistra
authors: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), Zernikedreef 9, 2333 CK Leiden, The Netherlands.
authors: Robert
authors: R
authors: Kleemann
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D002097:C-Reactive Protein / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology / Q000627:therapeutic use*; D004036:Diet, Atherogenic; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D002392:Catechin; D002097:C-Reactive Protein
keywords: Atherosclerosis; CRP; Epicatechin; Inflammation; NFκB; Polyphenol