Abstract 441: Epicatechin Attenuates Atherosclerosis and Exerts Anti-inflammatory Effects on Diet-Induced Human CRP and NfκB in vivo
Objective: Previous studies investigating flavanol-rich foods provided 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*3Leiden 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 (8w and 20w). 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*3Leiden 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.
Conclusion: 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.
Author Disclosures: M. Morrison: Research Grant; Significant; Top Institute Food and Nutrition. J.W. Van der Hoorn: None. R. Van der Heijden: Research Grant; Significant; Top Institute Food and Nutrition. P. Heeringa: None. E. Kaijzel: None. L. Verschuren: None. R. Blomhoff: None. T. Kooistra: None. R. Kleemann: None.
- © 2014 by American Heart Association, Inc.