Inflammatory macrophages in the kidney contribute to salt-sensitive hypertension

Fehrenbach, Daniel J.; Mattson, David L.

doi:10.1152/ajprenal.00454.2019

Cited by 24 publications

(16 citation statements)

References 35 publications

(34 reference statements)

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“…In terms of innate immunity, low inflammatory status in the body has been proved to stimulate immune regulation, leading to elevated blood pressure and related kidney damage, in which macrophages resident in the dermis can regulate salt sensitivity by affecting the storage of nonpermeable sodium in the skin [15]. Hypertonic state can also drive macrophages from anti-inflammatory phenotype to pro-inflammatory phenotype and then infiltrate the kidney in large quantities, release inflammatory factors, and cause kidney damage [16]. In cellular immunity, activated T lymphocytes have been illuminated to raise blood pressure by inducing oxidative stress injury and renal reabsorption of sodium.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Higher Blood Pressure and Worse Renal Function in Salt-Sensitive Hypertension

Chu¹,

Zhou²,

Lu³

et al. 2021

Kidney Blood Press Res

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Background: The underlying pathogenesis of patients with salt-sensitive hypertension expressing higher blood pressure and severer renal damage remains uncertain. Methods: We recruited 329 subjects, 131 in salt-sensitive (SS) group, 148 in nonsalt-sensitive (NSS) group, and 50 healthy people in normal group and tested their renal function, 24-h ambulatory blood pressure, and growth factor series. Results: The SS group showed worse renal function with lower estimated glomerular filtration rate and higher urinary microalbumin, α-microglobulin, urinary protein Cr ratio, and urinary immunoglobulin. Most indicators in 24-h ambulatory blood pressure of the SS group were significantly enhanced than the NSS group, indicating their higher blood pressure. The significantly elevated growth factors in the SS group were AR, BMP-5, EG-VEGF, GH, HGF, IGFBP-2, IGFBP-3, IGFBP-6, MCSFR, NT-4, PDGF-AA, SCF, SCFR, VEGFR2, VEGFR3, and VEGF-D, compared to other 2 groups or one of them. PI3K-AKT pathway was activated in the SS group. Conclusions: Differences in growth factors and pathways may account for the manifestations of the SS group. Activated PI3K-AKT pathway with higher IGFBP-3 and GH can lead to renal damage. Higher MCSFR in the SS group indicates that high blood pressure and severe kidney damage may be associated with the activation of the immune system. EG-VEGF, VEGFR2, VEGFR3, and VEGF-D can also explain the elevated blood pressure due to the dilated lymphatic system which drains excess sodium and water back into circulation. The SS group presented higher AR and HGF which may worsen renal function by regulating cell proliferation and tumor formation. However, due to the potential low awareness rate of hypertension at the very beginning, we cannot ensure the exact occurrence order of blood pressure, renal damage, and salt sensitivity. Therefore, further studies which can track data from the onset of hypertension are needed.

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of Higher Blood Pressure and Worse Renal Function in Salt-Sensitive Hypertension

Chu¹,

Zhou²,

Lu³

et al. 2021

Kidney Blood Press Res

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“…Dietary preferences can cause gastrointestinal microbiota imbalance and translocation, resulting in renal microcirculation disorders. For example, a high-salt diet can induce oxidative stress in the kidney, resulting in increased renal perfusion pressure and immune cell infiltration, thus leading to kidney damage ( 125 , 126 ). Meanwhile, under high-salt conditions, serum and glucocorticoid-regulated kinase 1 (SGK1)-mediated phosphorylation of forkhead box of transcription factors O1 (FOXO1) and forkhead box of transcription factors O3 (FOXO3) may lead to instability of Foxp3, thus reducing the inhibitory function of Treg cells ( 127 ) ( Figure 4B ).…”

Section: Renal Microenvironmentmentioning

confidence: 99%

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

Han

Tao

et al. 2022

Front. Immunol.

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Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

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“…Osteopetrotic (Op/Op) mice, in which macrophages are functionally deficient, exhibit reduced hypertension and vascular remodeling in response to Ang II or DOCA salt (De Ciuceis et al 2005 ; Ko et al 2007 ). For a more detailed overview of the role of monocyte/macrophages in hypertension and the possible mechanisms, see Fehrenbach and Mattson ( 2020 ) and Wenzel ( 2019 ).…”

Section: Innate Immune Cells In Hypertensionmentioning

confidence: 99%

Immune mechanisms in arterial hypertension. Recent advances

2021

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Increasing evidence indicates that hypertension and hypertensive end-organ damage are not only mediated by hemodynamic injury. Inflammation also plays an important role in the pathophysiology and contributes to the deleterious consequences of this disease. Cells of the innate immune system including monocyte/macrophages and dendritic cells can promote blood pressure elevation via effects mostly on kidney and vascular function. Moreover, convincing evidence shows that T and B cells from the adaptive immune system are involved in hypertension and hypertensive end-organ damage. Skin monocyte/macrophages, regulatory T cells, natural killer T cells, and myeloid-derived suppressor cells have been shown to exert blood pressure controlling effects. Sodium intake is undoubtedly indispensable for normal body function but can be detrimental when taken in excess of dietary requirements. Sodium levels also modulate the function of monocyte/macrophages, dendritic cells, and different T cell subsets. Some of these effects are mediated by changes in the microbiome and metabolome that can be found after high salt intake. Modulation of the immune response can reduce severity of blood pressure elevation and hypertensive end-organ damage in several animal models. The purpose of this review is to briefly summarize recent advances in immunity and hypertension as well as hypertensive end-organ damage.

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Inflammatory macrophages in the kidney contribute to salt-sensitive hypertension

Cited by 24 publications

References 35 publications

Pathogenesis of Higher Blood Pressure and Worse Renal Function in Salt-Sensitive Hypertension

Pathogenesis of Higher Blood Pressure and Worse Renal Function in Salt-Sensitive Hypertension

A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives

Immune mechanisms in arterial hypertension. Recent advances

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