TY - JOUR
T1 - Androgen increases AT1a receptor expression in abdominal aortas to promote angiotensin II-induced AAAs in apolipoprotein E-deficient mice
AU - Henriques, Tracy
AU - Zhang, Xuan
AU - Yiannikouris, Frederique B.
AU - Daugherty, Alan
AU - Cassis, Lisa A.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Objective - Castration of male apolipoprotein E-deficient (apoE) mice reduces angiotensin II (Ang II)-induced abdominal aorta aneurysms (AAAs) to that of female mice. The purpose of this study was to determine whether this reduction is attributable to androgen-mediated regulation of aortic Ang II type 1A receptors (AT1aR). Methods and Results - AT1aR mRNA abundance in the AAA-prone region of abdominal aortas was 8-fold greater compared to thoracic aortas of male but not female mice. AT1aR mRNA abundance decreased after castration in abdominal but not thoracic aortas of male mice. Dihydrotestosterone (DHT, 0.16 mg/d) administration to castrated male mice restored AT1aR mRNA abundance in abdominal aortas but had no effect in thoracic aortas. DHT also increased AT1aR mRNA abundance in abdominal aortas from female mice. Castrated male or female apoE mice were administered DHT during infusion of saline or Ang II (1000 ng/kg/min for 28 days). DHT administration did not alter serum cholesterol concentrations, lipoprotein distributions, or atherosclerotic lesion areas in either male or female mice. However, administration of DHT increased AAA incidence in male (27% placebo versus 75% DHT) and female mice (28% placebo versus 64% DHT). Conclusions - Androgen promotes AT1aR mRNA abundance in abdominal aortas associated with increased Ang II-induced AAAs.
AB - Objective - Castration of male apolipoprotein E-deficient (apoE) mice reduces angiotensin II (Ang II)-induced abdominal aorta aneurysms (AAAs) to that of female mice. The purpose of this study was to determine whether this reduction is attributable to androgen-mediated regulation of aortic Ang II type 1A receptors (AT1aR). Methods and Results - AT1aR mRNA abundance in the AAA-prone region of abdominal aortas was 8-fold greater compared to thoracic aortas of male but not female mice. AT1aR mRNA abundance decreased after castration in abdominal but not thoracic aortas of male mice. Dihydrotestosterone (DHT, 0.16 mg/d) administration to castrated male mice restored AT1aR mRNA abundance in abdominal aortas but had no effect in thoracic aortas. DHT also increased AT1aR mRNA abundance in abdominal aortas from female mice. Castrated male or female apoE mice were administered DHT during infusion of saline or Ang II (1000 ng/kg/min for 28 days). DHT administration did not alter serum cholesterol concentrations, lipoprotein distributions, or atherosclerotic lesion areas in either male or female mice. However, administration of DHT increased AAA incidence in male (27% placebo versus 75% DHT) and female mice (28% placebo versus 64% DHT). Conclusions - Androgen promotes AT1aR mRNA abundance in abdominal aortas associated with increased Ang II-induced AAAs.
KW - Androgen
KW - Aneurysms
KW - Angiotensin
KW - Atherosclerosis
KW - Sex hormones
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U2 - 10.1161/ATVBAHA.107.160382
DO - 10.1161/ATVBAHA.107.160382
M3 - Article
C2 - 18451329
AN - SCOPUS:46249083315
SN - 1079-5642
VL - 28
SP - 1251
EP - 1256
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 7
ER -