LPS-Stimulated Cytokine Production in Type I Cells Is Modulated by the Renin–Angiotensin System

Background. The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism.Methods and results. A panel of mouse models including mice lacking angiotensinogen,Agt(Agt-KO), mice expressingAgtsolely in adipose tissue (aP2-Agt/Agt-KO), and mice overexpressingAgtin adipose tissue (aP2-Agt) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased inAgt-KO mice, while plasma adiponectin levels were increased. aP2-Agtmice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2-Agtmice.Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

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Role of the renin-angiotensin system in the pathogenesis of preeclampsia

AJP Renal Physiology ◽

10.1152/ajprenal.00410.2003 ◽

2005 ◽

Vol 288 (4) ◽

pp. F614-F625 ◽

Cited By ~ 86

Author(s):

Dinesh M. Shah

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Receptor Activation ◽

Gravid Uterus ◽

Type I ◽

Hypertensive Disorder ◽

Angiotensin System ◽

Renin Angiotensin ◽

Organ Systems

Preeclampsia is a hypertensive disorder unique to pregnancy with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression observed both in human preeclampsia and in a transgenic mouse model with a human preeclampsia-like syndrome supports the concept that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. A novel disease paradigm of the two-kidney one-clip (2K-1C) Goldblatt model is presented for preeclampsia, wherein the gravid uterus is the clipped “kidney” and the two maternal kidneys represent the unclipped kidney. Validation of the 2K-1C Goldblatt model analogy requires evidence of elevated angiotensin II in the peripheral circulation before vascular maladaptation in preeclampsia. Convincing evidence of the elevation of angiotensin II in preeclampsia does not exist despite the fact that much of vascular pathogenesis appears to be due to angiotensin type I (AT1) receptor activation. Vascular maladaptation with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT1and bradykinin B2receptor heterodimerization and the production of an autoantibody against AT1. Various organ systems with a predilection for involvement in preeclampsia are each a site of a tissue-based RAS. How angiotensin II-mediated mechanisms may explain the primary clinical-pathological features of preeclampsia is described. Future investigations are proposed to more precisely define the role of activation of the uteroplacental RAS in the mechanisms underlying preeclampsia.

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The Renin-Angiotensin System: A Key Role in SARS-CoV-2- Induced COVID-19

Molecules ◽

10.3390/molecules26226945 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6945

Author(s):

George El-Arif ◽

Antonella Farhat ◽

Shaymaa Khazaal ◽

Cédric Annweiler ◽

Hervé Kovacic ◽

...

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Organ Damage ◽

World Health ◽

Electrolyte Balance ◽

Type I ◽

Related Factors ◽

Angiotensin System ◽

Mortality And Morbidity ◽

Renin Angiotensin

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin–angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.

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Transforming Growth Factor-β Blockade Down-Regulates the Renin-Angiotensin System and Modifies Cardiac Remodeling after Myocardial Infarction

Endocrinology ◽

10.1210/en.2008-0165 ◽

2008 ◽

Vol 149 (11) ◽

pp. 5828-5834 ◽

Cited By ~ 50

Author(s):

Leigh J. Ellmers ◽

Nicola J. A. Scott ◽

Satyanarayana Medicherla ◽

Anna P. Pilbrow ◽

Paul G. Bridgman ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Remodeling ◽

Transforming Growth Factor ◽

Ventricular Remodeling ◽

Specific Inhibitor ◽

Renin Angiotensin System ◽

Plasma Renin ◽

Type I ◽

Angiotensin System ◽

Renin Angiotensin

After myocardial infarction (MI), the heart may undergo progressive ventricular remodeling, resulting in a deterioration of cardiac function. TGF-β is a key cytokine that both initiates and terminates tissue repair, and its sustained production underlies the development of tissue fibrosis, particularly after MI. We investigated the effects of a novel orally active specific inhibitor of the TGF-β receptor 1 (SD-208) in an experimental model of MI. Mice underwent ligation of the left coronary artery to induce MI and were subsequently treated for 30 d after infarction with either SD-208 or a vehicle control. Blockade of TGF-β signaling reduced mean arterial pressure in all groups. SD-208 treatment after MI resulted in a trend for reduced ventricular and renal gene expression of TGF-β-activated kinase-1 (a downstream modulator of TGF-β signaling) and a significant decrease in collagen 1, in association with a marked decrease in cardiac mass. Post-MI SD-208 treatment significantly reduced circulating levels of plasma renin activity as well as down-regulating the components of the cardiac and renal renin-angiotensin system (angiotensinogen, angiotensin converting enzyme, and angiotensin II type I receptor). Our findings indicate that blockade of the TGF-β signaling pathway results in significant amelioration of deleterious cardiac remodeling after infarction.

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