Androgen receptor promotes abdominal aortic aneurysm development via modulating inflammatory interleukin-1α and transforming growth factor-β1 expression

Hypertension
Chiung-Kuei HuangChawnshang Chang

Abstract

Sex difference is a risk factor for abdominal aortic aneurysm (AAA) formation yet the reason for male predominance remains unclear. Androgen and the androgen receptor (AR) influence the male sex difference, indicating that AR signaling may affect AAA development. Using angiotensin II–induced AAA in apolipoprotein E null mouse models (82.4% AAA incidence), we found that mice lacking AR failed to develop AAA and aorta had dramatically reduced macrophages infiltration and intact elastic fibers. These findings suggested that AR expression in endothelial cells, macrophages, or smooth muscle cells might play a role in AAA development. Selective knockout of AR in each of these cell types further demonstrated that mice lacking AR in macrophages (20% AAA incidence) or smooth muscle cells (12.5% AAA incidence) but not in endothelial cells (71.4% AAA incidence) had suppressed AAA development. Mechanism dissection showed that AR functioned through modulation of interleukin-1α (IL-1α) and transforming growth factor-β1 signals and by targeting AR with the AR degradation enhancer ASC-J9 led to significant suppression of AAA development. These results demonstrate the underlying mechanism by which AR influences AAA development is through IL-1α ...Continue Reading

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Citations

Jan 16, 2016·The Journal of Endocrinology·Chiung-Kuei HuangChawnshang Chang
Apr 25, 2019·The Journal of Endocrinology·Bo-Kyung SonMasahiro Akishita
Aug 9, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jia ShiFan He
Sep 5, 2020·Journal of Cellular and Molecular Medicine·Mengdie ChengHui Xin
May 26, 2016·Molecular Medicine Reports·Yan-Feng LiuMing Qi
Oct 23, 2019·The Journal of Clinical Investigation·Caitlin J BowenHarry C Dietz
Jul 28, 2019·Molecular Reproduction and Development·Francesca MossaAlmudena Veiga-Lopez
Jul 20, 2019·Scientific Reports·Huimin YanChristine T N Pham
Oct 17, 2020·Journal of the American Heart Association·Nicole K AndersonHarry C Dietz
Oct 17, 2020·Journal of the American Heart Association·Yasushi TashimaMichael P Fischbein
Mar 24, 2020·Sexual Medicine·Omer Faruk KirlangicSerap Gur
Aug 10, 2021·Frontiers in Cardiovascular Medicine·Shin Mei ChanAlan Dardik
Feb 28, 2020·Atherosclerosis·Jaap G NeelsGiulia Chinetti

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