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Effects Of Androgen On The Expression Of Androgen Receptor And Platelet Derived Growth Factor Receptor-β In Vascular Smooth Muscle Tissues And Cells

Posted on:2003-07-16Degree:MasterType:Thesis
Country:ChinaCandidate:H S LvFull Text:PDF
GTID:2144360092465622Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Coronary heart disease (CHD) is a leading cause of mortality. Numerous clinical and epidemiological reports demonstrate that men are generally more susceptible to CHD than their female counterparts. Increasing evidence indicates that estrogen has a favorable effect on female cardiovascular protecting and atherogenic decreasing. Much less work,however,has addressed the possible effects of androgens on atherogenesis,and the minimal existing experimental and clinical data are conflicting,showing variously that androgen had either positive effects or no on the process of atherosclerosis (AS). Vascular smooth muscle cells (VSMCs) proliferation has definite pathophysiological roles in atherogenesis and the development of restenosis. Growth factors such as platelet-derived growth factor (PDGF) released from activated platelets,smooth muscle cells (SMCs),and monocytes,interacting with the PDGF- P receptor (PDGFR- P ),is an important mediator of SMCs proliferation and migration. Because recent evidence suggests the existence of androgen receptors (AR) in VSMCs,the potential modulation of AR and PDGFR- P expression in VSMCs by androgen is of obvious interest. The present study undertaken try to explore the effects of androgen on the expression of AR and PDGFR- P in aortic vascular smooth muscle tissues and cells,in order to reveal the possible protective mechanism of AR on male. Methods1. Ten young male rats (young group). Fourty aged male rats were randomly divided into four groups:aged group,the other groups received androgen replacement treatment,intramuscular injection of testosterone enanthate (TE) once a week for TE concentrations at 2.5mg/kg 5.0mg/kg and 10.0 mg/kg,respectively. All animals were fed freely during the 16-week treatment period. The expression of AR and PDGFR- P in aortic vascularsmooth muscle tissues were studied by Western blot.2. VSMCs were cultured from male rat thoracic aorta by using the explant method. Effects of testosterone at different concentrations with or without its antagonist flutamide on the expression of AR and PDGFR- P by Western blot. Results1. Average serum TC LDL-C and VLDL-C were higher in aged group than that of in young group (P<0.05);After aged rats were received androgen hormone replacement treatment,average serum TC and LDL-C in higher dose group decreased significantly (P<0.01) .2. The expression of AR in aged group rats' vascular smooth muscle tissue was reduced to 68% compared with young group (P<0.01);Also the expression of AR in mid-dose aged group rats' vascular smooth muscle tissue was 1.25 fold higher than that of in aged group (P<0.01),but was still reduced to 84% compared with young group (P<0.05 ) .3. The expression of PDGFR- P in aged group rats' vascular smooth muscle tissue was 2.13 fold higher than that of in young group (P<0.01);Compared with aged group,the expression of PDGFR- & in mid-dose aged rats' vascular smooth muscle tissue was reduced to 50% and that of 1.25 fold higher in high dose group (P<0.01) .4. The expression of AR was 1.63 fold higher and reduced to 47% for testosterone at concentrations of 10-7M and 10-5M,respectively,for 12 hours in VSMC compared with control group (P<0.05);10-5 M flutamide alone didn't effect the expression of AR;10-7M testosterone together with 10-5M flutamide inhibited the stimulatory effect induced by testosterone at 10-7M;The expression of AR weren't difference at the same concentration for 12 hours and for 24 hours.5. The expression of PDGFR-B was 1.21 fold higher and reduced to 76% for testosterone at concentrations of 10-5M and 10-6M,respectively,for 12 hours in VSMC than that of control group (P<0.05);Also the expression of PDGFR-B was reduced to 78% and 40% after 10-7 M testosterone stimulated for 12 hours and 24 hours,respectively,whencompared with control group (P<0.01);10-5M flutamide alone didn't effect the expression of PDGFR-P;10-7M testosterone together with 10-5M flutamide inhibited the stimulatory effect induced by testosterone at 10'7M. Conclusion1...
Keywords/Search Tags:receptors, androgen, platelet-derived growth factors, vascular smooth muscle, coronary heart disease, atherosclerosis, flutamide, western blot
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