Progesterone attenuates hypertension and autoantibody levels to the angiotensin II type 1 receptor in response to elevated cadmium during pregnancy

Zhang, Qiong; Huang, Yu; Zhang, Keke; Yan, Yan; Wu, Jie; Wu, Fan; Zhao, Yuan; Xu, Hua; Jiang, Wei; Yu, Danyang; Chen, Yongtao; Ye, Duyun

doi:10.1016/j.placenta.2017.12.004

Cited by 29 publications

(24 citation statements)

References 33 publications

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“…These two concepts were united in a previous report showed that serum from PE women contain autoantibodies that bind and activate angiotensin II type 1 receptor (AT1R) 10 . Increasing studies from us and others [7][8][9][10][11][12][13] have shown that PE is a pregnancy-induced autoimmune disease in which key features of the disease result from the autoantibody, termed angiotensin II type 1 receptor autoantibody (AT1-AA). However, previous works have been restricted to confirmation of its pathophysiological relevance to PE and have been unable to specifically clarify the mechanisms for determining AT1-AA production.…”

Section: Introductionmentioning

confidence: 99%

Lipoxin A4 suppresses angiotensin II type 1 receptor autoantibody in preeclampsia via modulating caspase-1

Liu

Cheng

et al. 2020

Cell Death Dis

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Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality. Numerous studies have shown that women with PE develop autoantibody, termed angiotensin II type 1 receptor autoantibody (AT1-AA), and key features of the disease result from it. Emerging evidence has indicated that inflammatory cell necrosis, such as pyroptosis, could lead to autoantigen exposure and stimulate autoantibody production. Caspase-1, the central enzyme of inflammasome and key target of pyroptosis, may play roles in AT1R exposure and AT1-AA production. Exploring endogenous regulator that could inhibit AT1-AA production by targeting pyroptosis will be essential for treating PE. Lipoxin A 4 (LXA 4), endogenous dual anti-inflammatory and proresolving lipid mediator, may inhibit AT1-AA production via modulating caspase-1. Thus, we explore whether caspase-1 is essential for AT1-AA production and LXA 4 inhibits AT1-AA via modulating caspase-1. PE patients and mice developed AT1-AA associated with caspase-1 activation. Caspase-1 deletion leaded to AT1-AA decrease in PE mice. Consistent with these findings, we confirmed caspase-1 activation, trophoblast pyroptosis and AT1R exposure in PE mice and trophoblast model, while caspase-1 deficiency showed decreased trophoblast pyroptosis and AT1R exposure in vitro and in vivo. Interestingly, LXA 4 could suppress AT1-AA production via regulating caspase-1 as well as enhancing phagocytosis of dead trophoblasts by macrophages. These results suggest that caspase-1 promotes AT1-AA production via inducing trophoblast pyroptosis and AT1R exposure, while LXA 4 suppresses AT1-AA production via modulating caspase-1, supporting caspase-1 serving as a therapeutic target for attenuating AT1-AA and LXA 4 protecting patients from AT1-AA and PE.

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Section: Introductionmentioning

confidence: 99%

Lipoxin A4 suppresses angiotensin II type 1 receptor autoantibody in preeclampsia via modulating caspase-1

Liu

Cheng

et al. 2020

Cell Death Dis

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“…Various animal models are used for experimental studies of sexual and reproductive dysfunction, although rodent models are the most common (Amaral et al, ; Zhang et al, , ). Most of these models present morphological, physiological, and hormonal differences compared to humans, such as different hormonal profiles, polyovulation, and multiple pregnancies, among others.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the uterine hormonal control of the bat Artibeus lituratus during the different phases of its reproductive cycle

Santiago

Albernaz

Santos

et al. 2020

Journal of Morphology

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Artibeus lituratus is a frugivorous bat that directly assists in the restoration of degraded habitats through the effective dispersion of seeds and fruits. Given its great importance, this work aimed to evaluate the uterine hormonal control of A. lituratus during its different reproductive phases. The uteri of 30 sexually mature adult females, five specimens for each of the six sample groups (NON, nonreproductive; P1, initial pregnancy; P2, intermediate pregnancy; P3, advanced pregnancy; LAC, lactating; P + LAC, pregnant‐lactating), were submitted to analyses of serum estradiol and progesterone concentrations, in addition to immunohistochemical analyses. Both estradiol and progesterone, gradually increased during pregnancy, with a marked significant increase in P3 females. Both returned to low levels in LAC‐females; however, estradiol levels decreased further in P + LAC‐females, while progesterone increased in the same group. In general, signs indicative of aromatase expression were observed in the endometrium of all analyzed groups and in the placenta of bats in the gestation groups. Similarly, ERα and PR were expressed in the myometrium, endometrium and placenta at varying levels of intensity. The results indicate that the uterine microenvironment of A. lituratus is directly regulated by serum concentrations of estradiol and progesterone, and fluctuations in these concentrations control morphological and physiological changes of this organ during different phases of the reproductive cycle. Research highlights Increases in serum concentrations of estradiol and progesterone coordinate the gestational period of A. lituratus. Estradiol activates ERα, stimulating cell proliferation in the uterus, in addition to activating the expression of PR, which trigger the quiescence of the myometrium and stimulation of the secretion and differentiation of the endometrium. Results showed several similarities to humans, indicating the use of A. lituratus as an animal model in reproductive studies.

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“…Unlike our findings in OVX females, AT1R radioligand binding was not altered in HC-treated females. One possible mechanism for this is that OVX leads to decreased levels of both estrogen and progesterone, the latter of which also has been shown to decrease AT1R binding 48,49 ; however, since levonorgestrel also reduces levels of both ovarian hormones, progesterone is not likely playing a role in the differential effects of HC and OVX on AT1R binding. Rather, these two treatments are likely modulating the RAS through different mechanisms, possibly in a hormone dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Estradiol modulation of the renin–angiotensin system and the regulation of fear extinction

et al. 2019

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Post-traumatic stress disorder (PTSD) is more prevalent in women than men, yet much remains to be determined regarding the mechanism underlying this sex difference. Clinical and preclinical studies have shown that low estradiol levels during extinction of fear conditioning in rodents (i.e., cue exposure therapy in humans) leads to poor extinction consolidation and increased fear during extinction recall. The renin–angiotensin system (RAS) is also associated with stress-related pathologies, and RAS antagonists can enhance extinction consolidation in males. However, less is known about how estradiol and the RAS converge to alter fear extinction consolidation in females. Since estradiol downregulates the RAS, we determined the role of surgically (via ovariectomy [OVX]) and pharmacologically (via the hormonal contraceptive [HC], levonorgestrel) clamping estradiol at low levels in female rats on fear-related behavior, serum estradiol and angiotensin II (Ang II) levels, and angiotensin II type I receptor (AT1R) binding in the brain. We then tested whether the AT1R antagonist losartan would alter fear-related behavior in an estradiol-dependent manner. We found that both OVX and HC treatment produced extinction consolidation deficits relative to intact female rats in proestrus (when estradiol levels are high), and that losartan treatment mitigated these deficits and reduced freezing. OVX, but not HC, altered AT1R ligand binding, though HC reduced estradiol and increased Ang II levels in plasma. These findings have significant clinical implications, indicating that administration of an AT1R antagonist, especially if estradiol levels are low, prior to an exposure therapy session may improve treatment outcomes in females.

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Progesterone attenuates hypertension and autoantibody levels to the angiotensin II type 1 receptor in response to elevated cadmium during pregnancy

Cited by 29 publications

References 33 publications

Lipoxin A4 suppresses angiotensin II type 1 receptor autoantibody in preeclampsia via modulating caspase-1

Lipoxin A4 suppresses angiotensin II type 1 receptor autoantibody in preeclampsia via modulating caspase-1

Evaluation of the uterine hormonal control of the bat Artibeus lituratus during the different phases of its reproductive cycle

Estradiol modulation of the renin–angiotensin system and the regulation of fear extinction

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