2024-03-29T08:15:29Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/52432022-07-04T13:20:57Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
Poulsen, Christian Bo
author
Mortensen, Martin Bodtker
author
Koechling, Wolfgang
author
Sorensen, Charlotte Brandt
author
Bentzon, Jacob F
funder
Ferring Pharmaceuticals
2017-10-30T13:32:26Z
2017-10-30T13:32:26Z
2016
J Am Heart Assoc. 2016; 5(2):e002800
2047-9980
http://hdl.handle.net/20.500.12105/5243
26908406
10.1161/JAHA.115.002800
Journal of the American Heart Association
Background-Treatment of prostate cancer often involves androgen deprivation therapy (ADT) by gonadotropin-releasing hormone (GnRH) receptor agonists, GnRH receptor antagonists, or orchiectomy. ADT may increase the rate of cardiovascular disease events, but recent clinical studies suggested that not all means of ADT carry the same risk, raising the possibility of non-testosterone-mediated effects of different forms of ADT on atherosclerosis. Here we compared effects of ADT on atherosclerosis in intact and orchiectomized Apoe-deficient mice. Methods and Results-Chow-fed Apoe-deficient mice were allocated to orchiectomy and/or monthly injections with the GnRH receptor agonist leuprolide or the GnRH receptor antagonist degarelix. Atherosclerosis was quantified at 26 weeks of age in the aortic arch by en face examination and in the aortic root by histology. In intact Apoe-deficient mice, all types of ADT reduced testosterone production to castration levels. Although hypercholesterolemia was accentuated in leuprolide-treated mice, the amount and composition of atherosclerosis was not different between the different types of ADT. In orchiectomized Apoe-deficient mice, leuprolide, but not degarelix, augmented hypercholesterolemia, changed body, thymus, and spleen weights, and increased atherosclerosis in the aortic root. No direct effects of the drugs were detectable on cytokine secretion from murine bone marrow-derived macrophages or on splenocyte proliferation. Conclusions-No differences in the development of atherosclerosis were detected among groups of intact Apoe-deficient mice treated with different types of ADT. A pro-atherogenic, possibly cholesterol-mediated, effect of leuprolide was seen in orchiectomized mice that might be relevant for understanding the potential cardiovascular risk associated with GnRH agonist-based ADT.
eng
Androgen deprivation therapy
Atherosclerosis
Inflammation
Testosterone
GONADOTROPIN-RELEASING-HORMONE
PROSTATE-CANCER
CARDIOVASCULAR-DISEASE
GNRH RECEPTOR
MURINE LUPUS
MOUSE MODEL
ATHEROSCLEROSIS
RISK
MEN
EXPRESSION
Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice
journal article
URL
https://repisalud.isciii.es/bitstream/20.500.12105/5243/1/DifferencesInHypercholesterolemiaAndAtherogenesis_2016
File
MD5
d306d4acdfc21309172b518f5a5b543e
1396206
application/pdf
DifferencesInHypercholesterolemiaAndAtherogenesis_2016
URL
https://repisalud.isciii.es/bitstream/20.500.12105/5243/10/DifferencesInHypercholesterolemiaAndAtherogenesis_2016.txt
File
MD5
37936068515667f81c5c84ee9ec17b02
50516
text/plain
DifferencesInHypercholesterolemiaAndAtherogenesis_2016.txt