Female apolipoprotein E-deficient mice are protected against the development of endothelial dysfunction with ageing

Abstract

Endothelial dysfunction is one of major factors leading to the development of atherosclerosis. Female animals are less susceptible to atherosclerosis. The present study investigated whether or not there is a gender difference in the degree of endothelial dysfunction during the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mouse is a well developed animal model in which atherosclerosis is established at about 24 weeks of age. Endothelium-dependent relaxations to acetylcholine were examined in aortae and superior mesenteric arteries isolated from ApoE-deficient mice of both genders at 8 and 32 weeks. Acetylcholine-induced nitric oxide (NO)-mediated relaxations in the aorta and mesenteric arteries were comparable in young male and female ApoE-deficient mice. In aged ApoE-deficient mice, the NO-mediated relaxations of the aorta and mesenteric arteries were reduced significantly only in the male gender. Similarly, the degree of endothelium-derived hyperpolarizing factors (EDHF)-mediated relaxations in mesenteric arteries of young ApoE-deficient mice was not different between male and female. However, the EDHF-mediated relaxation was abolished in aged male mice, but only partially reduced in aged female mice. Thus, the present findings indicate that during ageing female atherosclerotic-prone mice animals are protected from the impairment of both NO- and EDHFmediated relaxations. The better endothelial function in aged female ApoE-deficient mice may contribute to the protection against the development of atherosclerosis.