Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Henriques, Tracy A.; Zhang, Xuan; Yiannikouris, Frédérique; Daugherty, Alan; Cassis, Lisa A.

doi:10.1161/atvbaha.107.160382

Cited by 99 publications

(118 citation statements)

References 46 publications

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“…75 Castrated male mice and rats treated with dihydrotestosterone and testosterone, respectively, showed a significant increase in the incidence of AAA compared with only castrated males. 69,76 Recently, a study by the same group showed that castration reduced the progressive lumen dilatation of established AAAs, suggesting that androgens also play a role in the progression of AAAs in male mice and that TGFb and Serpine1 may be targets of testosterone action in the progression of AAA. 77 In Vitro Studies Using Cultured SMCs Woodrum et al 78 examined sex differences of MMP2 in rat aortic SMCs (RASMCs).…”

Section: The Effect Of Castration On Aaa Parametersmentioning

confidence: 99%

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Makrygiannis

Courtois

Drion

et al. 2014

Annals of Vascular Surgery

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Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in men, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature, we examined human and animal in vivo and in vitro studies to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17b-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in men and women, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.

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Section: The Effect Of Castration On Aaa Parametersmentioning

confidence: 99%

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Makrygiannis

Courtois

Drion

et al. 2014

Annals of Vascular Surgery

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“…Previous studies in our laboratory demonstrated that testosterone is a primary mediator of higher AAA prevalence in adult AngII-infused male mice, as orchiectomy decreased AAA incidence to the level of adult females [32]. Additional studies demonstrated a greater abundance of AT1aR mRNA in abdominal compared to thoracic aortas of male, but not female Apoe -/-mice [32].…”

Section: Inluences Of Sex Hormones On Aaa Development and Progressionmentioning

confidence: 58%

“…Additional studies demonstrated a greater abundance of AT1aR mRNA in abdominal compared to thoracic aortas of male, but not female Apoe -/-mice [32]. Moreover, castration of male mice decreased AT1aR mRNA abundance in abdominal aortas, which was restored when castrated male mice were administered dihydrotestosterone [32].…”

Section: Inluences Of Sex Hormones On Aaa Development and Progressionmentioning

confidence: 92%

“…Our laboratory demonstrated previously that sex hormones are primary contributors to higher AAA susceptibility in male compared to female apoliproprotein E deicient (Apoe -/-) mice, as ovariectomy had no efect on AAA formation while orchiectomy decreased AAA incidence to the level of females [31,32]. We also demonstrated that testosterone promotes AAA incidence in male and female mice associated with increased expression of angiotensin receptor 1a (AT1aR) expression speciically in abdominal aortas [32]. Similarly, in the elastase perfusion AAA model, male rats had larger and more frequent AAAs than females [33].…”

Section: Sex Diferences In Aaa Prevalence In Human and Experimental Mmentioning

confidence: 96%

“…In addition to efects of endogenous sex hormones, exogenous administration of estrogen inhibited AAA development and/or progression in AngII-infused male mice, while exogenous dihydrotestosterone administration also promoted AngII-induced AAAs in females [32,37,[39][40][41][42]. Mechanisms of estrogen to protect against AAA formation and/or progression are multifactorial.…”

Section: Inluences Of Sex Hormones On Aaa Development and Progressionmentioning

confidence: 99%

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Sexual Dimorphism of Abdominal Aortic Aneurysms

Alsiraj¹,

Thatcher²,

Cassis³

2017

Aortic Aneurysm

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Sex is the largest nonmodiiable risk factor for the development of abdominal aortic aneurysms (AAAs) in humans and experimental models. Data from several studies consistently demonstrate a higher AAA prevalence in males than in females, contributing to divergent recommendations for AAA screening in men and women. Despite a higher AAA prevalence in males, females have more rapid rates of aneurysm dilation, and aneurysms rupture at smaller sizes. Unfortunately, no therapies have been efective to retard aneurysm dilation in either sex. Results from experimental AAA models indicate a protective role for estrogen in AAA development and progression, while male testosterone has been demonstrated to markedly promote angiotensin II (AngII)-induced AAAs. Potential mechanisms implicated in sex hormone regulation of AAAs include regulation of inlammation, matrix metalloproteinases, aromatase activity, oxidative stress, stem cells, and transforming growth factor-beta. In addition to sex hormones, sex chromosomes have been implicated in diseases of the aorta. Turner's syndrome (monosomy X) patients have a high incidence of thoracic aortic rupture. Recent studies indicate a novel approach to deine the relative role of sex hormones versus sex chromosomes in experimental AAAs. Further studies are warranted to determine interactions between sex hormones and sex chromosomes in AAA development and progression.

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Aortic aneurysm: pathophysiology and therapeutic options

Yang,

Khan,

Liang

et al. 2024

MedComm

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Aortic aneurysm (AA) is an aortic disease with a high mortality rate, and other than surgery no effective preventive or therapeutic treatment have been developed. The renin–angiotensin system (RAS) is an important endocrine system that regulates vascular health. The ACE2/Ang‐(1–7)/MasR axis can antagonize the adverse effects of the activation of the ACE/Ang II/AT1R axis on vascular dysfunction, atherosclerosis, and the development of aneurysms, thus providing an important therapeutic target for the prevention and treatment of AA. However, products targeting the Ang‐(1–7)/MasR pathway still lack clinical validation. This review will outline the epidemiology of AA, including thoracic, abdominal, and thoracoabdominal AA, as well as current diagnostic and treatment strategies. Due to the highest incidence and most extensive research on abdominal AA (AAA), we will focus on AAA to explain the role of the RAS in its development, the protective function of Ang‐(1–7)/MasR, and the mechanisms involved. We will also describe the roles of agonists and antagonists, suggest improvements in engineering and drug delivery, and provide evidence for Ang‐(1–7)/MasR's clinical potential, discussing risks and solutions for clinical use. This study will enhance our understanding of AA and offer new possibilities and promising targets for therapeutic intervention.

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Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Cited by 99 publications

References 46 publications

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Sexual Dimorphism of Abdominal Aortic Aneurysms

Aortic aneurysm: pathophysiology and therapeutic options

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