NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage

Bruder‐Nascimento, Thiago; Ferreira, Nathanne S.; Zanotto, Camila Ziliotto; Ramalho, Fernanda Naira Zambelli; Pequeno, Isabela O.; Olivon, Vânia C.; Neves, Karla B; Alves-Lopes, Rhéure; Campos, Eduardo Geraldo de; Silva, Carlos Alberto A.; Fazan, Rubens; Carlos, Daniela; Mestriner, Fabíola; Prado, Douglas da Silva; Pereira, Felipe Valença; Braga, Tárcio Teodoro; Luiz, João; Cau, Stefany B.A.; Elias, Paula Condé Lamparelli; Moreira, Ayrton Custódio; Câmara, Niels Olsen Saraiva; Zamboni, Dario S.; Alves‐Filho, José C.; Tostes, Rita C.

doi:10.1161/circulationaha.116.024369

Cited by 86 publications

(84 citation statements)

References 48 publications

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“…An increasing number of reports indicated that Ald could stimulate macrophages infiltrate into the kidneys during disease [1,8,29]. In this study, we confirmed that there were infiltrating macrophages into the contralateral kidneys; moreover, those macrophages produce NLRP3, which is consistent with previous studies [17]. These results suggest that macrophages may participate in renal cell pyroptosis in kidney injury.…”

Section: Discussionsupporting

confidence: 92%

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Eplerenone Ameliorates Cell Pyroptosis in Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction

Chang

Xiong

et al. 2019

Nephron

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Background: The progression of chronic renal failure in patients with unilateral renal injury is associated with loss of function in the contralateral kidney, but the molecular mechanism remains unclear. The activation of mineralocorticoid receptor (MR) in the kidney contributes to renal cell damage, leading to apoptosis, pyroptosis, and necrosis. Pyroptosis is a programmed cell death induced by caspase-1, which is usually activated by nod-like receptor pyrin-containing 3 (NLRP3) inﬂammasomes. Our study aimed to investigate the effects of eplerenone (EPL) on cell pyroptosis in the contralateral kidneys of unilateral ureteral obstruction (UUO) rats. Methods: Sprague-Dawley rats were randomly divided into 3 groups: sham group, UUO group (10 days of left ureter ligation), and UUO treated with EPL (UUO + EPL) group. The contralateral kidneys of all rats were collected for studies. Results: We observed evidently increased number of pyroptosis cells in the contralateral kidneys of UUO rats compared to those from Sham rats. The expression of NLRP3, caspase-1, interleukin-1β, serum and glucocorticoid-inducible protein kinase-1, and nuclear factor kappa B were also upregulated in the contralateral kidneys of UUO rats compared to Sham kidneys, and these effects were reduced by MR blocker EPL. Conclusion: Our data suggest that the activation of MR is involved in NLRP3/caspase-1 pathway-induced cell pyroptosis in the contralateral kidney of UUO model.

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Section: Discussionsupporting

confidence: 92%

“…Early studies suggested that Ald-induced NLRP3 is possibly released from macrophages [17]. According to this, we detected F4/80, a marker of macrophages, with immunohistochemistry.…”

Section: Epl Reduced Nlrp3 Secretion In Macrophages In the Contralatementioning

confidence: 51%

Eplerenone Ameliorates Cell Pyroptosis in Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction

Chang

Xiong

et al. 2019

Nephron

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“…For example, constitutively activated NLRP3 causes inflammation and abnormal skeletal development in mice (Bonar et al., ). On the other hand, NLRP3 knockout mice are protected against ischaemic kidney injury (Kim et al., ) and aldosterone‐induced vascular damage (Bruder‐Nascimento et al., ). Thus, the relevance of the inflammasome on periodontal bone loss needs further investigations.…”

Section: Preamblementioning

confidence: 99%

Osteoimmunology: Inflammatory osteolysis and regeneration of the alveolar bone

Gruber

2019

J Clinic Periodontology

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Aim Osteoimmunology covers the cellular and molecular mechanisms responsible for inflammatory osteolysis that culminates in the degradation of alveolar bone. Osteoimmunology also focuses on the interplay of immune cells with bone cells during bone remodelling and regeneration. The aim of this review was to provide insights into how osteoimmunology affects alveolar bone health and disease. Method This review is based on a narrative approach to assemble mouse models that provide insights into the cellular and molecular mechanisms causing inflammatory osteolysis and on the impact of immune cells on alveolar bone regeneration. Results Mouse models have revealed the molecular pathways by which microbial and other factors activate immune cells that initiate an inflammatory response. The inflammation‐induced alveolar bone loss occurs with the concomitant suppression of bone formation. Mouse models also showed that immune cells contribute to the resolution of inflammation and bone regeneration, even though studies with a focus on alveolar socket healing are rare. Conclusions Considering that osteoimmunology is evolutionarily conserved, osteolysis removes the cause of inflammation by provoking tooth loss. The impact of immune cells on bone regeneration is presumably a way to reinitiate the developmental mechanisms of intramembranous and endochondral bone formation.

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“…Clinical trials have shown the beneficial effects of ALDO antagonists in chronic heart failure and postmyocardial infarction treatment (Lother et al 2015). Long-term infusion of mineralocorticoid (ALDO) in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities (Bruder-Nascimento et al 2016). Androgens enhance skeletal muscle mass by promoting the enlargement of skeletal muscle cells (SinhaHikim et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Plasma Steroids and Cardiorespiratory Fitness Response to Regular Exercise

Rankinen

Leon

et al. 2017

Research and Perspectives in Endocrine Interactions

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The aim of this report is to evaluate the relationships between baseline levels of adrenal, gonadal and conjugated steroids and baseline cardiorespiratory fitness, as assessed by maximal oxygen uptake (VO 2 max), as well as its response to a standardized exercise program. To address this aim we used a subset of the HERITAGE Family Study (N = 448). In men, significant positive associations were found between baseline VO 2 max/kg weight and plasma levels of androsterone glucuronide (ADTG), dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone binding globulin (SHBG), and testosterone (TESTO), and negative association with aldosterone (ALDO). In women, only the free androgen index (FAI) was negatively associated with baseline VO 2 max/kg weight. Neither baseline plasma steroid levels nor SHBG concentrations were associated with the gains in VO 2 max resulting from exposure to the 20-week aerobic exercise program after adjustment for baseline values, age and ethnicity (white or black). We conclude that baseline plasma steroid levels are only weakly associated with individual differences in cardiorespiratory fitness in the sedentary state in men but not in women, whereas no association could be detected with trainability, as defined by the change in VO 2 max with the exercise program.

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NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage

Abstract: Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels.

Cited by 86 publications

References 48 publications

Eplerenone Ameliorates Cell Pyroptosis in Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction

Eplerenone Ameliorates Cell Pyroptosis in Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction

Osteoimmunology: Inflammatory osteolysis and regeneration of the alveolar bone

Plasma Steroids and Cardiorespiratory Fitness Response to Regular Exercise

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