VASCULAR AND MOLECULAR EFFECTS OF ENDOGENOUS ANDROGENS IN AN ATHEROSCLEROTIC EXPERIMENTAL RABBIT MODEL

Introduction. The effects of androgens on atherosclerosis and its clinical manifestations are controversial. The objective of this study was to compare the morphologic and functional characteristics and gene expression associated with reverse metabolism of cholesterol in castrated and non-castrated atherosclerotic rabbits. Methods. Forty male NZ rabbits were distributed in four groups: 1: non-castrated with a normal diet; 2: castrated with a normal diet; 3: non-castrated with an atherogenic diet, and 4: castrated with an atherogenic diet. Measurements of total cholesterol, free testosterone, in vitro vascular relaxation, histomorphometric analyses of the thoracic aorta and expression of the IL-1 beta, LRX-alpha and ABCA1 genes were carried out in each rabbit. Results. Castration decreased levels of total testosterone (2.1 +/- 0.3 vs. 0.8 +/- 0.4 ng/mL; P=.024). In animals with a normal diet (groups 1 and 2), castration increased expression of IL-1 beta (0.71 +/- 0.07 vs. 0.77 +/- 0.06; P<.001), decreased that of LXR-alpha (0.77 +/- 0.008 vs. 0.41 +/- 0.01; P<.001) and increased that of ABCA1 (0.2 +/- 0.008 vs. 0.31 +/- 0.08; P<.001). In animals with an atherogenic diet (groups 3 and 4), castration was associated with a larger plaque area (0.9 +/- 1.3 vs. 2.6 +/- 2.3 mm(2); P=.026), plaque area/vessel area ratio (0.08 +/- 0.1 vs. 0.25 +/- 0.1; P<.001), plaque area/media area ratio (0.2 +/- 0.2 vs. 0.4 +/- 0.3; P=.003), greater expression of IL-1 beta (0.93 +/- 0.05 vs. 1.1 +/- 0.02; P<.001), reduction of LXR-alpha (1.45 +/- 0.01 vs. 1.29 +/- 0.01; P<.001), and reduction of ABCA1 (0.22 +/- 0.1 vs. 0.20 +/- 0.02; P<.001). Conclusions. This study shows that in the presence of atherosclerosis induced by hypercholesterolemia, endogenous testosterone could have an attenuating or protective effect on atherogenesis.