Growing evidences support that androgen displays beneficial effects on cardiovascular functions although the mechanism of androgen actions remains to be elucidated. Modulation of endothelial cell growth and function is a potential mechanism of androgen actions. We demonstrated in the present study that androgens [dihydrotestosterone (DHT) and testosterone], but not 17β-estradiol, produced a time- and dose-dependent induction of cell proliferation in primary human aortic endothelial cells (HAECs) as evident by increases in viable cell number and DNA biosynthesis. Real-time qRT-PCR analysis showed that DHT induced androgen receptor (AR), cyclin A, cyclin D1, and vascular endothelial growth factor (VEGF) gene expression in a dose- and time-dependent manner. The addition of casodex, a specific AR antagonist, or transfection of a specific AR siRNA blocked DHT-induced cell proliferation and target gene expression, indicating that the DHT effects are mediated via AR. Moreover, coadministration of SU5416 to block VEGF receptors, or transfection of a specific VEGF-A siRNA to knockdown VEGF expression, produced a dose-dependent blockade of DHT induction of cell proliferation and cyclin A gene expression. Interestingly, roscovitine, a selective cyclin-dependent kinase inhibitor, also blocked the DHT stimulation of cell proliferation with a selective inhibition of DHT-induced VEGF-A expression. These results indicate that androgens acting on AR stimulate cell proliferation through upregulation of VEGF-A, cyclin A, and cyclin D1 in HAECs, which may be beneficial to cardiovascular functions since endothelial cell proliferation could assist the repair of endothelial injury/damage in cardiovascular system.
Background: The aim of this study was to estimate the relationship between arterial stiffness and components of metabolic syndrome (MetS) in different age- and gender groups.Methods: A total of 12,900 Chinese adults aged 20-79 years were recruited and stratified on the basis of gender and age. All participants underwent the measurement of waist circumference, blood pressure (BP), brachial-ankle pulse wave velocity (baPWV; an indicator of arterial stiffness), and blood chemistry. Multiple linear regression analysis was performed to evaluate the relationship between baPWV and above variables, to determine the relative influence of each component of MetS on baPWV.Results: The prevalence of metabolic disorders except for low high-density lipoprotein cholesterol (HDL-C) was much higher in men than in women. All participants with MetS or any component of MetS except for low HDL-C had higher baPWV. BP was positively correlated with baPWV in all groups, while HDL-C was not correlated with baPWV in any groups. In addition, fasting glucose was related to baPWV in middle-aged adults and the elderly. Waist circumference had a positive association with baPWV in middle-aged adults and young men, triglyceride levels showed a significant correlation with baPWV in middle-aged women and young men. Of the MetS components, elevated BP was the strongest predictor of baPWV.Conclusion: The prevalence of metabolic disorders and the association between baPWV and metabolic variables are dependent on age and gender. Different components of MetS exert distinct impacts on the baPWV in different age- and gender groups, with BP being the strongest predictor. It is suggested that age and gender should be taken into accounted in the management of MetS aiming to reduce subsequent complications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.