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 (V) over bar (CV)/(V) over bar (PCV), where (V) over bar (CV) and (V) over bar (PCV) 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.111Ysciescopu

Immunological consequences of ageing microvascular hemodynamic changes in view of cancer development and treatment

Risk factors of cardiovascular diseases have long been implicated as risk factors for carcinogenesis, but clear explanations for their association have not been presented. In this article, fundamental concepts from carcinogenesis, microvascular hemodynamics, and immunity are collectively reviewed and analyzed in context of the known features of vascular ageing effects, in formulating a theory that suggests reduced microvascular immunity as an important driving factor for carcinogenesis. Furthermore, scientific, preclinical, and clinical evidence that support this new theory are presented in an interdisciplinary manner, offering new explanations to previously unanswered factors that impact cancer risks and its treatment outcome such as chronic drug use, temperature, stress and exercise effects among others. Forward-looking topics discussing the implications of this new idea to cancer immunotherapeutics are also discussed.11Nsciescopu