Sustained Delivery of Dihydrotestosterone Impact on the Pathophysiology of Isolated Endothelial and Smooth Muscle Cells

Abstract

Sex steroid hormones appear to be a risk factor for the development of atherosclerosis. Proliferation of vascular smooth muscle cells (SMC) was documented to be a mediator in atherosclerotic plaque formation. The objective of this study was to investigate the effect of sustained delivery of dihydrotestosterone (DHT) on the growth of cultured aortic endothelial cells (EC) and SMC incubated individually, or in combination. The SMC were explanted from the media and intima of the abdominal and thoracic aorta of adult male rabbits, and EC were prepared by trypsinization of the vessel. Cells were seeded and grown undisturbed for up to 6 weeks in culture. A total of four equal (n=4 wells) groups was used in Phase I. Groups 1–3 were plated with EC, SMC, and EC+SMC, respectively. Group IV served as control. Half of the wells (n=4 per group) in each group were exposed to tricalcium phosphates capsules loaded with 40 mg DHT (release profile: 3–5 ng/ml/day) and second half was exposed to sham capsules. Resultes revealed that sustained release of DHT to EC+SMC cultures induced greater cellular proliferation than in control wells, as determined by cell counts after 96 hours of culture. In contrast, the number of cells/well of a single cell type, grown in the presence of DHT, did not differ from the control wells. In the second phase of this investigation, various capsules releasing different concentrations of DHT were used. The release rate of 10 ng/ml/day of DHT regressed the proliferation rate by approximately 40% compared to other lower doses (2.4, or 6 ng/ml/day). Results of this investigation suggest that: (1) sustained delivery of a physiological dose of DHT to combined cultures of EC+SMC significantly increased cellular growth, while the exposure of DHT to EC or SMC grown individually had no effect on the rate of cellular proliferation, and (2) the effect of sustained delivery of DHT on vascular smooth muscle cells was found to be dose dependent.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.