Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt‐induced hypertension in mice

Krishnan, Shalini M; Dowling, Jennifer K.; Ling, Yeong Hann; Diep, Henry; Chan, Christopher T.; Ferens, Dorota; Kett, Michelle M; Pinar, Anita A.; Samuel, Chrishan S.; Vinh, Antony; Arumugam, Thiruma V.; Hewitson, Tim D.; Kemp-Harper, Barbara K; Robertson, Avril A. B.; Cooper, Matthew A.; Latz, Eicke; Mansell, Ashley; Sobey, Christopher G.; Drummond, Grant Raymond

doi:10.1111/bph.13230

Cited by 151 publications

(162 citation statements)

References 64 publications

(94 reference statements)

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“…Using a mouse model of renin angiotensin system (RAS)-mediated hypertension, Crowley and coworkers discovered that interleukin (IL)-1 receptor signaling impairs the ability of intra-renal macrophages to facilitate tubular Na + excretion [30]. Excess aldosterone [31] as well as the treatment of uninephrectomized mice with deoxycorticosterone acetate and saline to drink [32] result in overproduction of IL-1β and thereby might impact on renal Na + handling. Together, these data suggest that RAS blockade might promote the macrophage’s accessory function of assisting tubular Na + excretion in addition to its ability to block inflammation and fibrosis (reviewed in [33]).…”

Section: Salt Gradients In the Kidney And Their Impact On Mononuclearmentioning

confidence: 99%

Elementary immunology: Na+ as a regulator of immunity

et al. 2016

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The skin can serve as an interstitial Na+ reservoir. Local tissue Na+ accumulation increases with age, inflammation and infection. This increased local Na+ availability favors pro-inflammatory immune cell function and dampens their anti-inflammatory capacity. In this review, we summarize available data on how NaCl affects various immune cells. We particularly focus on how salt promotes pro-inflammatory macrophage and T cell function and simultaneously curtails their regulatory and anti-inflammatory potential. Overall, these findings demonstrate that local Na+ availability is a promising novel regulator of immunity. Hence, the modulation of tissue Na+ levels bears broad therapeutic potential: increasing local Na+ availability may help in treating infections, while lowering tissue Na+ levels may be used to treat, for example, autoimmune and cardiovascular diseases.

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Section: Salt Gradients In the Kidney And Their Impact On Mononuclearmentioning

confidence: 99%

Elementary immunology: Na+ as a regulator of immunity

et al. 2016

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“…It has been found that inflammatory cytokines, IL-1β and IL-18, in plasma and vessels are increased in hypertension [23]. Inflammasome is essential for one kidney/deoxycorticosterone acetate/salt-induced hypertension in mice [24]. Hydrogen sulfide suppresses high glucose-induced cardiomyocyte inflammation by inhibiting the TLR4/NF-κB pathway and its downstream NLRP3 inflammasome activation [25].…”

Section: Introductionmentioning

confidence: 99%

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

Ren

Tong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Angiotensin (Ang) II plays vital roles in vascular inflammation and remodeling in hypertension. Phenotypic transformation of vascular smooth muscle cells (VSMCs) is a major initiating factor for vascular remodeling. The present study was designed to determine the roles of NLRP3 inflammasome activation in Ang II-induced VSMC phenotypic transformation and vascular remodeling in hypertension. Methods: Primary VSMCs from the aorta of NLRP3 knockout (NLRP3^-/-) mice and wild-type (WT) mice were treated with Ang II for 24 h. Subcutaneous infusion of Ang II via osmotic minipump for 2 weeks was used to induce vascular remodeling and hypertension in WT and NLRP3^-/- mice. Results: NLRP3 gene deletion attenuates Ang II-induced NLRP3 inflammasome activation, phenotypic transformation from a contractile phenotype to a synthetic phenotype and proliferation in primary mice VSMCs. Ang II-induced hypertension and vascular remodeling in WT mice were attenuated in NLRP3^-/- mice. Furthermore, Ang II-induced NLRP3 inflammasome activation, phenotypic transformation and proliferating cell nuclear antigen (PCNA) upregulation were inhibited in the media of aorta of NLRP3^-/- mice. Conclusions: NLRP3 inflammasome activation contributes to Ang II-induced VSMC phenotypic transformation and proliferation as well as vascular remodeling and hypertension.

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“…Furthermore, ASC −/− mice or mice treated with NLRP3 inhibitor MCC950 were protected from 1K/DOCA/salt-induced HTN, inflammation, and fibrosis 65 . NLRP3 inflammasome involvement has also been established in animal models of SSHTN and was first shown by Qi et al where Dahl SS rats fed a high salt diet resulted in elevated NLRP3 and IL-1β in the hypothalamic paraventricular nucleus (PVN), which was inhibited by NFκB blockade, indicating the importance of localized PVN NFκB activation in the sympathoexcitation that leads to HTN in response to high salt 66 .…”

Section: Targets Of Innate Immunitymentioning

confidence: 94%

Novel adaptive and innate immunity targets in hypertension

Abais‐Battad

Dasinger

Fehrenbach

et al. 2017

Pharmacological Research

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Hypertension is a worldwide epidemic and global health concern as it is a major risk factor for the development of cardiovascular diseases. A relationship between the immune system and its contributing role to the pathogenesis of hypertension has been long established, but substantial advancements within the last few years have dissected specific causal molecular mechanisms. This review will briefly examine these recent studies exploring the involvement of either innate or adaptive immunity pathways. Such pathways to be discussed include innate immunity factors such as antigen presenting cells and pattern recognition receptors, adaptive immune elements including T and B lymphocytes, and more specifically, the emerging role of T regulatory cells, as well as the potential of cytokines and chemokines to serve as signaling messengers connecting innate and adaptive immunity. Together, we summarize these studies to provide new perspective for what will hopefully lead to more targeted approaches to manipulate the immune system as hypertensive therapy.

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Inflammasome activity is essential for one kidney/deoxycorticosterone acetate/salt‐induced hypertension in mice

Cited by 151 publications

References 64 publications

Elementary immunology: Na+ as a regulator of immunity

Elementary immunology: Na+ as a regulator of immunity

NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling

Novel adaptive and innate immunity targets in hypertension

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