A growing body of evidence suggests that endothelial dysfunction plays a crucial role in all stages of atherosclerosis. Numbers of circulating endothelial progenitor cells (EPC) and endothelial microparticles (EMP) are emerging as novel markers of endothelial dysfunction and CVD risk; low numbers of EPCs indicate limited repair of the endothelium, and high numbers of EMPs indicate endothelial damage.( Reference Sen, McDonald, Coates and Bonder 1 , Reference Dignat-George and Boulanger2 ) In addition, the Glu298Asp (or 894G→T) polymorphism in the eNOS gene has been associated with CVD and reduced endothelial function, although it is not clear whether this affects EPC or EMP numbers( Reference Casas, Cavalleri and Bautista 3 ). However, recent data suggests that supplementation of n-3 PUFA significantly improves endothelial function( Reference Wang, Liang and Wang 4 ). Therefore, the aim of the present study was to investigate the effect of fish oil supplementation on the EPC and EMP levels in individuals prospectively genotyped for the Glu298Asp polymorphism.
A double-blinded, randomized, placebo-controlled, cross-over trial was performed in 91 non-smoking healthy adults (21–65 y), at moderate risk for CVD, who were genotyped for the eNOS Glu298Asp polymorphism and assigned to a GG (n=46) or GT/TT (n=45) group. Subjects were randomized onto either fish oil (1.8 g/d n-3 PUFA) or placebo (corn oil) for 8 weeks, followed by an 8-week washout and cross-over to the other treatment for another 8 weeks. Plasma EPC and EMP levels were measured by flow cytometry at the beginning and end of each supplementation phase. EPC and EMP were defined as CD34+KDR+ and CD42b-CD31+, respectively, and were expressed as absolute numbers using TruCOUNT tubes.
Change in EPC (left) and EMP (right) counts after 8-week treatment with placebo (A) or fish oil (B).
Supplementation with fish oil significantly increased numbers of circulating EPC (P=0.019), but decreased numbers of EMP (P<0.001) compared with the control period. However, there was no influence of eNOS genotype (P=0.49 and 0.32 for EMP and EPC, respectively; linear mixed model). The current study therefore indicates that n-3 LC-PUFA might improve endothelial function by modulating endothelial damage and repair, regardless of the eNOS genotype of the individual.
This work was supported by the Nutricia Research Foundation.
