Mitochondria can orchestrate sex differences in cell fate of vascular smooth muscle cells from rats

BACKGROUND: In basal conditions, vascular smooth muscle cells freshly isolated from aortas of male and female rats display marked sex differences in terms of redox balance and susceptibility to ultraviolet radiation-induced cell death. In particular, in the same experimental conditions, cells from male rats are more susceptible to oxidative stress and underwent apoptosis, while cells from female rats underwent premature senescence. In the present work, the mechanism involved in cell fate after ultraviolet radiation exposure is investigated. METHODS: Vascular smooth muscle cells, isolated from the descending aortas of both female and male Sprague–Dawley young rats, were exposed to a single sub-cytotoxic dose of ultraviolet radiation (200 mJ/cm(2)). The distribution and the expression of molecules involved in cell survival and mitochondrial physiology were evaluated by static and flow cytometry using commercial kits and antibodies. Statistical analyses were performed by using Student’s t test and two-way ANOVA. RESULTS: After exposure to ultraviolet radiation, an upregulation of survival proteins such as Bclx(L), survivin and the presence in the nucleus of NF-κB were found in cells from females. Conversely, pro-apoptotic proteins such as Bax, caspase-3, and caspase-9 as well as loss of mitochondrial membrane potential were found in cells from male rats. CONCLUSIONS: Our results suggest that (i) mitochondria, being producers of ROS, can orchestrate sex differences in cell fate of VSMC and (ii) mitochondrial dysfunction may be a significant mechanism by which cardiovascular risk factors lead to the formation of vascular lesions in a sex-specific way.