Homocysteine-induced peripheral microcirculation dysfunction in zebrafish and its attenuation by L-arginine

Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter [Formula: see text], where [Formula: see text] and [Formula: see text] represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively. The ratio of the peripheral microcirculation perfusion to the systemic perfusion is largely decreased due to peripheral accumulation of neutrophils, while the systemic perfusion is relatively preserved by increased blood supply from subintestinal vein. Pretreatment with L-arginine attenuates the effects of Hcy on peripheral microcirculation and reduces the peripheral accumulation of neutrophils. Given its convenience, high reproducibility of the observation site, non-invasiveness, and the ease of drug treatment, the present zebrafish model with the proposed parameters will be used as a useful drug screening platform for investigating the pathophysiology of Hcy-induced microvascular diseases.