Background and Aims: 
Homoarginine (HA) is an emerging biomarker with low levels associated with increased risk of cardiovascular disease (CVD) in epidemiological studies. Recently, we identified HA supplementation to be beneficial in murine models of ischemic stroke and chronic heart failure. However, the underlying mechanism remains elusive. As both CV entities share atherosclerosis as an underlying pathology, we hypothesize that HA supplementation may protect against atherosclerosis.
Methods: 
Hyperlipidemic mice were pre-treated with 14 mg/L HA-enriched water (ApoE-HA) or normal drinking water (ApoE) for two weeks prior to the start of a 6 week western diet period, and the treatment continued throughout the duration of the diet. Innate and adaptive immune cells were analyzed using flow cytometry. Atherosclerotic plaque size and composition were determined using histochemistry.
Results:
Dietary HA supplementation reduced atherosclerotic plaque formation in ApoE-mice by 22% in the aortic root (p<0.01). Phenotypically, plaques were more initial, as ApoE-HA mice showed fewer fibrous cap atheromas and more intimal xanthomas and pathological intimal thickenings than the ApoE mice (p<0.05). Flow cytometric analysis of leukocyte populations pointed out a T cell specific effect of HA supplementation with CD3+ T cells and the fraction of CD4+ T cells being significantly reduced in blood (p<0.01) and spleen (p<0.01) of ApoE-HA mice. Accordingly, in vitro proliferation of isolated CD4+ T cells from ApoE-HA mice was significantly decreased compared to the ApoE control group (p<0.05).
Conclusions: 
HA supplementation prevents atherogenesis potentially via modulating T cell reactivity.  Further mechanistic studies are merited to validate HA as a potential therapeutic for CVD.

05 - HOMOARGININE SUPPLEMENTATION AMELIORATES ATHEROSCLEROSIS