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Plasma hyaluronic acid is increased in peripheral arterial disease and altered by fish oil supplementation

Published online by Cambridge University Press:  14 October 2011

J. Madden ,
C. Shearman ,
R. F. Grimble  and
P. C. Calder
J. Madden
Affiliation:
Department of food and Nutritional Sciences, University of Reading, RG6 6AP, UK
C. Shearman
Affiliation:
Developmental origins of health and disease, University of Southampton, SO16 6YD, UK
R. F. Grimble
Affiliation:
Developmental origins of health and disease, University of Southampton, SO16 6YD, UK
P. C. Calder
Affiliation:
Developmental origins of health and disease, University of Southampton, SO16 6YD, UK
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Abstract

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Abstract
Information
Proceedings of the Nutrition Society , Volume 70 , Issue OCE4: Summer Meeting, 4–6 July 2011, 70th Anniversary: From plough through practice to policy , 2011 , E162
Copyright
Copyright © The Authors 2011

Hyaluroinic acid (HA) is an intra-cellular matrix polymer whose main functions are structural and the maintenance of tissue hydration. The catabolism of the HA polymer to smaller subunits is initiated in membrane lipid rafts and is dependent on CD44(Reference Noble1). These smaller subunits are released into circulation and are thought to be proinflammatory as plasma levels increase in acute inflammatory conditions such as septicaemia(Reference Noble1). Plasma HA levels are also a strong indicator of severe liver fibrosis as fibrotic cytokines such as TGF and FGF enhance HA catabolism(Reference Avila, Carmo and Farah Kde2).

We hypothesised that circulating HA levels would be increased in peripheral arterial disease (PAD) as this disease it is known to have both fibrotic and inflammatory components. Furthermore, as fish oil supplementation has been shown to reduce inflammation and monocyte CD44 expression(Reference Madden, Shearman and Dunn3), we investigated the effect of supplementation of 1.7 g EPA+DHA per day for 12 weeks on plasma HA levels in 72 PAD patients.

In 83 healthy controls, we found plasma HA levels to be low (mean 1.54 ng/ml±1.35), whereas in 72 PAD patients plasma HA levels were much higher (mean 19.75 ng/ml±3.76) (P<0.001). Following fish oil supplementation in the PAD group plasma HA levels increased (mean 27.03 ng/ml±5.64) (P=0.02).

One possible mechanism for these findings is that fish oil has previously been shown to increase expression of a splice variant form of CD44, CD44v3, on PAD monocytes(Reference Madden, Shearman and Dunn3). CD44v3 can bind fibrotic cytokines such as TGF and FGF, and may increase their potency leading to increased fibrosis and stabilisation of atherosclerotic plaques(Reference Thies, Garry and Yaqoob4).

Another explanation is that increased circulating HA levels are often seen in high-volume blood loss and thought to act as a intravascular volume expander, so preventing circulatory collapse. In vascular compromised individuals, increased levels of HA may enhance circulatory competence which we have previously demonstrated for fish oil supplementation in PAD(Reference Madden, Brunner and Dastur5).

References

1.Noble, PW (2002) Matrix Biol 21, 25e9.CrossRefGoogle Scholar
2.Avila, RE, Carmo, RA, Farah Kde, P et al. (2010) JR Braz J Infect Dis 14, 335–341.CrossRefGoogle Scholar
3.Madden, J, Shearman, CP, Dunn, RL et al. (2009) Nutr Metab Cardiovasc Dis 19, 247–252.CrossRefGoogle Scholar
4.Thies, F, Garry, JM, Yaqoob, P et al. (2003) Lancet 361, 477–485.CrossRefGoogle Scholar
5.Madden, J, Brunner, A, Dastur, ND et al. (2007) Prostaglandins, Leukotriens and essential fatty acids 76, 331–340.CrossRefGoogle Scholar