Dietary Supplementation with Homoarginine Preserves Cardiac Function in a Murine Model of Post-Myocardial Infarction Heart Failure
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Low plasma homoarginine (HA) is an emerging biomarker for cardiovascular disease and an independent predictor of mortality in patients with heart failure.1 Plasma levels appear to reflect cardiac dysfunction, positively correlating with ejection fraction and inversely with circulating brain natriuretic peptide.2 However, whether this outcome is a bystander or cause-and-effect has yet to be established. Within the context of stroke, a direct causal relationship has been inferred because normal mice pretreated with 14 mg/L HA had a smaller stroke size.3 In the present study, we show for the first time that dietary supplementation with HA improves cardiac function in the setting of chronic heart failure, suggesting a novel preventive strategy and inferring that low HA levels may be inherently detrimental because of a loss of this effect.
We first confirmed that oral supplementation of C57BL/6J mice (Harwell, UK) with 14 mg/L L-HA hydrochloride (Sigma-Aldrich) in the drinking water for 4 weeks increased HA concentrations in both plasma (0.29±0.03 vs 0.89±0.07 µmol/L) and myocardial tissue (17.6±2.7 vs 48.8±6.8 nmol/g protein; n=5–10; P<0.01 for both), demonstrating a strong correlation between levels in plasma and myocardium (r=0.74, P<0.01). This dose did …