A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage

Norlander, Allison E.; Saleh, Mohamed A.; Pandey, Arvind K.; Itani, Hana A.; Wu, Jing; Xiao, Liang; Kang, Jooeun; Dale, Bethany L.; Goleva, Slavina; Laroumanie, Fanny; Du, Liping; Harrison, David G.; Madhur, Meena S

doi:10.1172/jci.insight.92801

Cited by 95 publications

(74 citation statements)

References 36 publications

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“…48 Recently, it was demonstrated that mice with CD4 + T-cell-restricted deficiency in Sgk1 are resistant to angiotensin II-induced hypertension and vascular inflammation. 49 Similar experiments in Il17a-deficient mice suggest the involvement of T H 17 cells in promoting hypertension. 50 IL-17 and IFN-c were found to be elevated in patients with symptoms of coronary artery atherosclerosis, supporting a role for T cells as mediators of vessel damage in humans.…”

Section: Salt-mediated Immune Cell Modulation and Its Role In Diseasementioning

confidence: 86%

“…Only T cell transfer into Rag −/− mice induces hypertension symptoms as observed in wild‐type controls . Recently, it was demonstrated that mice with CD4 + T‐cell‐restricted deficiency in Sgk1 are resistant to angiotensin II‐induced hypertension and vascular inflammation . Similar experiments in Il17a ‐deficient mice suggest the involvement of T H 17 cells in promoting hypertension .…”

Section: Salt‐mediated Immune Cell Modulation and Its Role In Diseasementioning

confidence: 89%

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The role of salt for immune cell function and disease

Willebrand

Kleinewietfeld

2018

Immunology

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The immune system evolved to protect organisms from invading pathogens. A network of pro- and anti-inflammatory cell types equipped with special effector molecules guarantees efficient elimination of intruders like viruses and bacteria. However, imbalances can lead to an excessive response of effector cells incurring autoimmune or allergic diseases. An interplay of genetic and environmental factors contributes to autoimmune diseases and recent studies provided evidence for an impact of dietary habits on the immune status and related disorders. Western societies underwent a change in lifestyle associated with changes in food consumption. Salt (sodium chloride) is one component prevalent in processed food frequently consumed in western countries. Here we summarize recent advances in understanding the mechanisms behind the effects of sodium chloride on immune cells like regulatory T cells (Tregs) and T helper (T ) 17 cells and its implication as a risk factor for several diseases.

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Section: Salt-mediated Immune Cell Modulation and Its Role In Diseasementioning

confidence: 86%

Section: Salt‐mediated Immune Cell Modulation and Its Role In Diseasementioning

confidence: 89%

The role of salt for immune cell function and disease

Willebrand

Kleinewietfeld

2018

Immunology

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“…Furthermore, knockout of T cells as well as Nox2 inactivation is protective from ANG II-induced thrombus formation (936). Involvement of T cell SGK1 in ANG II-induced hypertension and end organ damage has also been demonstrated (758). ␥␦ T cells appears to mediate ANG II-induced hypertension, vascular injury, and T cell activation in mice (109).…”

Section: Ang II Signaling In T Lymphocytesmentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

735

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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“…IL-17 способен инициировать синтез TNFα, IL-6, хемокинов, металлопротеиназ. В эксперименте доказан механизм повышения АД и развитие сосудистого ремоделирования за счет активации данных цитокинов [43,48].…”

Section: Introductionunclassified

Role of immunological disorders, endothelial dysfunction and hemostatic disorders in the genesis of arterial hypertension in the metabolic syndrome

2020

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Mortality from diseases of the circulatory system is a challenge for the modern health care. Arterial hypertension (AH) mostly contributes to development of cardiovascular complications. It often proceeds against the background of metabolic disorders. Pathogenesis of hypertension is currently being considered a multifactorial disease. Pathogenesis of hypertension certainly has distinct features in presence of metabolic disorders,. Therefore, it is relevant to summarize current literature on the role of immunological disorders, endothelial dysfunction and hemostatic disorders in AH genesis during metabolic syndrome (MS). Most authors agree with existence of several mechanisms that determine relationships between AH and insulin resistance. Development of hypertension in MS patients with is a consequence of immunometabolic processes. Abdominal obesity is an important component of MS. It is associated with chronic inflammation of visceral adipose tissue, its excessive infiltration by immune cells, and increased production of adipokines and cytokines (TNFα, IL-6) with hypertension. AH is associated with a significant increase in T cells, that mediate endothelial dysfunction (ED) and provide a link between hypertension and subsequent atherosclerosis. T lymphocytes trigger a cascade of reactions. IL-17 is the end product of these events It is involved not only in increasing blood pressure, but also contributes to the development of vascular wall stiffness in АН patients. Thus, the relationship between several types of immune cells leads to inflammatory reactions, including those of vascular wall, initiating endothelial dysfunction. Chronic non-specific inflammation in MS, supported by the cytokine system, is a triggering mechanism for ED progression. Excessive production of endothelin-1 and inhibition of nitric oxide production are the classic markers of ED. Immune damage leads to imbalance in the production of vasoconstrictor and vasodilating substances, proliferative and antiproliferative factors in endothelium. It was shown that ED is an integral aspect of the insulin resistance syndrome in pathogenesis of arterial hypertension associated with metabolic disorders, and contributes to its worsening, increased vascular reactivity and further AH development. According to modern studies, it has been shown that excessive synthesis of pro-inflammatory cytokines introduces disturbances in the system of vascular hemostasis. When studying the effects of metabolic disorders upon hemostatic system, we may conclude that activation of fibrinolytic and plasma chains occurs in the same way for both men and women, with small gender characteristics of individual components. The rheological properties of the blood are also changed with developing MS. Systematization of the available literature data on the issue under study can serve as a basis for determining prognostic criteria of hypertension progression and risk of thrombotic complications.

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A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage

Cited by 95 publications

References 36 publications

The role of salt for immune cell function and disease

The role of salt for immune cell function and disease

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Role of immunological disorders, endothelial dysfunction and hemostatic disorders in the genesis of arterial hypertension in the metabolic syndrome

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