A sex-related difference in the hypertrophic versus hyperplastic response of vascular smooth muscle cells to repeated passaging in culture

Activation of growth of vascular smooth muscle cells (VSMC) in adults parti cipates in pathogenesis of dysplastic diseases of the vascular system. In t his study, we examined the impact of gender of rat donors on the degree of hyperplastic and hypertrophic responses of VSMC in cultures subjected to re peated passaging. The cells were derived from the outgrowth zone of explant s of the thoracic aorta and were studied up to passage 45. Under these cond itions, the cells undergo repeated growth stimulation by the serum growth f actors mimicking some pathological situations in vivo. At lower passages (5 -7), the cells from both sex donors did not differ significantly in their d oubling time, maximum population density, protein content and ploidy. At hi gher passages (40-45), we found that the hyperplastic response, monitored b y doubling time and BrdU-revealed DNA synthesis, was more intense in VSMC o f male origin. In contrast, female-derived cells reacted by more prominent hypertrophic changes. The latter included a relatively higher increase in t he volume and protein content of cells. As indicated by the DNA content his tograms and chromosome numbers, these cells also showed a higher degree of passage-dependent polyploidization. In addition, the female-derived VSMC we re found to be more effective in adhesion to the growth support evidenced b y wider spreading and higher resistance of these cells to trypsin-mediated detachment as well as higher expression of some integrin and cytoskeletal m olecules. These features could partly account for the slower proliferation and polyploidization of these cells. The results suggest that rat VSMC popu lations of male and female origin contain cells which are intrinsically dif ferent with respect to their capability of reacting to growth stimuli. The lower responsiveness of female-derived cells to growth stimuli may contribu te to less frequent formation of hyperplastic vascular lesions in female or ganisms.