| BackgroundAge-adjusted morbidity and mortality rates from coronary artery disease (CAD) are higher in men than in women. The mechanism of gender difference in CAD is still not clarified. Coronary atherosclerosis increases with age, whilst a marked fall in serum bioavailable testosterone levels is observed. A considerable body of emerging evidence suggests that androgen deficiency contributes to the onset, progression, or both of cardiovascular disease (CVD). However, there is still no definite conclusion on their interacting pathways for lacking of large scale epidemic and controlled clinical studies. The effect of androgen on vasculature is mediated by androgen receptor (AR), which has a polymorphic CAG repeat in exon 1. The number of CAG repeats is inversely related to the transcriptional activity of AR. Therefore, we hypotheses that the correlation of endogenous androgen with CAD perhaps interacts with AR CAG repeat sequence polymorphism.Aimi To investigate the relationship between endogenous androgen level and coronary artery disease (CAD) in elderly men.ii To investigate whether or not AR CAG repeats correlate with coronary artery disease (CAD) in elderly men?iii If yes, how about the potential mechanism?PatientsWe screened all males patients aged 60 or older undergoing coronary angiography for diagnostic and interventional procedure in five separate centers during April 2009 to January 2010. Patients with prostate. cancer, elevated PSA (> 4ng/ml), on treatment with testosterone or estradiol were excluded. Finally,296 cases meeting the inclusive criteria were enrolled. Significant CAD was diagnosed in 237 patients by the presence of≥50% diameter reduction of the luminal diameter of≥1 coronary artery; 54 patients had 1-vessel disease,74 had 2-vessel disease and 109 had 3-vessel disease. Patients with angiographic normal or with less than 50% stenosis were assigned to the control group (59 cases).MethodsSerum FT, TT, E2, LH, FSH, SHBG and DHEA level were measured in all participants. Peripheral lymphocytes AR expression was assessed with Flow Cytometry (FCM). Gene fragment containing AR CAG repeat sequence polymorphism was amplified by PCR with specific fluorescent labeled primers. ABI 3730xl 384-capillary DNA analyzer was employed to identify the size of PCR products. After compared with the internal standard, we caculated the CAG repeats number for each PCR product.ResultsWe found no significant difference of FT, TT, E2, LH, FSH, SHBG and DHEA level in two groups, as well as lymphocytes AR expression level. FT and lymphocytes AR expression level inversely related to age. Patients with DM, obeses or hypertension often accompanied with much lower FT, TT or SHBG than that of corresponding contol. The AR CAG repeats number in CAD group was significantly lower than that of control. The serum FT level in Short AR group (CAG repeats< 22) is dramatically lower than that of long AR group. Multiple variables analysis showed that age, short AR positively associated with CAD, but FT inversely and independently associated with CAD. The correlation of shot AR with CAD in this population is independent on modulating peripheral lymphocyte AR expression.ConclusionWe concluded that low endogenous androgen might directly, or via exacerbating traditional cardiovascular risk factors indirectly promote the development of CAD in elderly males. Short AR increases AR transcriptional activity, along with decreased serum FT level, without changing the AR expression of lymphocytes, which maybe the potential mechanism of short AR relating to CAD in elderly male.
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