A Mouse Model for the Study of Vascular Permeability Changes Induced by Arsenic

Abstract

The primary objective of our present research was to develop an animal model for the investigation of arsenic-induced vasculopathy. Epidemiological evidence indicated that, aside from cancer, cardiovascular-related diseases were probably the most prominent health concerns in arseniasis areas. Although there were many investigations on the effect of arsenic on endothelial cells, most of these studies were conducted under in vitro conditions. A good animal model for studying the effects of arsenic on vascular integrity in vivo is very much needed. We have previously developed a rat model that could be used to demonstrate vascular changes induced by arsenic in vivo. In the present report, we are introducing a new model that is even more sensitive, economical, and effective than our original rat model. Taking advantage of the characteristics of mouse ears (thin, delicate, and with easily visible blood vessels), we demonstrated the pattern and extent of vascular leakage induced by arsenic clearly, quantitatively and convincingly. With this model, we demonstrated a time-dependent increase in vascular permeability induced by arsenic (a fourfold increase in vascular leakage was observed between 10–60 minutes). With this model, we were also able to demonstrate that small caliber vessels were more vulnerable than vessels of larger caliber. Thus, this animal model can provide dynamic information (from toxic effects, pathology, and functional alterations to cellular/molecular mechanisms) that cell culture techniques are unable to provide. The introduction of this model hopefully will stimulate and inspire many other new in vivo investigations on vasculopathy induced by arsenic or other chemicals in the future.