Circulating blood cells modulate the atherosclerotic process in apolipoprotein E-deficient mice.

The interaction of blood with the arterial tree may play an important role in the development of atherosclerotic lesions. The aims of this study were (1) to determine how anemia or increased hematocrit affect the development of atherosclerosis and (2) to find relationships between hematologic and hemorrheologic variables in apolipoprotein (apo) E-deficient mice. Forty-two mice were randomly divided into 3 groups of 14 mice each. There was no further manipulation in the control group. To induce anemia, the mice from one of the groups were repeatedly bled, drawing approximately 250 microL blood from each mouse twice a week. To increase the hematocrit levels in another group of mice, we injected 20 U recombinant human erythropoietin every other day. The development of lesions and the main variables involved in atherogenesis were compared among groups. Our results show that atherosclerosis was attenuated in the mice that were bled, and this was not accounted for by changes in plasma lipid levels, the distribution of lipoprotein particles, the body iron distribution, or oxidation parameters. Moreover, atherosclerosis was enhanced in the mice treated with the continuous administration of erythropoietin. To ascertain the relationship between hematocrit and whole blood viscosity, we measured both variables in pooled blood from 24 additional mice, which were manipulated to ensure a wide range of values. We found a direct and significant correlation between hematocrit and blood viscosity and between hematocrit and lesion size. Our data support in vivo the idea that hemorrheology has an important role in atherogenesis in this particular animal model.