Role of the receptor Mas in macrophage-mediated inflammation in vivo

Hammer, Anna; Yang, Guang; Friedrich, Juliane; Kovács, Ágnes Zsófia; Lee, Dong Hoon; Grave, Katharina; Jörg, Stefanie; Alenina, Natalia; Grosch, Janina; Winkler, Jürgen; Gold, Ralf; Bäder, Michael; Manzel, Arndt; Rump, Lars Christian; Müller, Dominik N.; Linker, Ralf A.; Stegbauer, Johannes

doi:10.1073/pnas.1612668113

Cited by 65 publications

(78 citation statements)

References 39 publications

(35 reference statements)

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“…Histopathological analyses at study end of the spinal cords of mice treated with the optimal dose of A(1-7) demonstrated that the improvements in clinical EAE disease course correlated with reductions in demyelination, axonal loss and immune infiltration. In a recent study by Hammer et al (2016) prophylactic once daily SQ administration of AVE0991, a selective Mas receptor agonist, 3 days prior to immunization with MOG, significantly reduced EAE disease incidence with a slightly ameliorated clinical EAE course (Hammer et al, 2016). Interestingly, whilst not observed in the present study, the Hammer et al (2016) publication also demonstrated that EAE disease course was significantly exacerbated in Mas receptor knockout mice.…”

Section: Discussioncontrasting

confidence: 54%

“…In a recent study by Hammer et al (2016) prophylactic once daily SQ administration of AVE0991, a selective Mas receptor agonist, 3 days prior to immunization with MOG, significantly reduced EAE disease incidence with a slightly ameliorated clinical EAE course (Hammer et al, 2016). Interestingly, whilst not observed in the present study, the Hammer et al (2016) publication also demonstrated that EAE disease course was significantly exacerbated in Mas receptor knockout mice. Previous studies by others have also revealed the importance of pharmacological intervention and the RAS pathway in MS as blockade of Ang-II signaling by ACE1 inhibitors or AT1R antagonists reduced the clinical severity of EAE (Platten et al, 2009;Stegbauer et al, 2009).…”

Section: Discussioncontrasting

confidence: 54%

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Reduced disease severity following therapeutic treatment with angiotensin 1–7 in a mouse model of multiple sclerosis

Lund

Stone

Levy

et al. 2019

Neurobiology of Disease

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Section: Discussioncontrasting

confidence: 54%

Section: Discussioncontrasting

confidence: 54%

Reduced disease severity following therapeutic treatment with angiotensin 1–7 in a mouse model of multiple sclerosis

Lund

Stone

Levy

et al. 2019

Neurobiology of Disease

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“…Our demonstration of the Mas receptor‐dependent inhibition of M1 macrophage differentiation by AVE0991 may extend the potential usefulness of this compound to a number of conditions in which M1 macrophages play a key role (Hammer et al , ). This includes pulmonary remodelling, inflammation and right ventricular hypertrophy in models of allergic asthma (Rodrigues‐Machado et al , ), as well as its protective effects in stroke (Lee et al , ) or liver cirrhosis (Klein et al , ).…”

Section: Discussionmentioning

confidence: 61%

Anti‐atherosclerotic effect of the angiotensin 1–7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis

Skiba

Nosalski

Mikołajczyk

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEInflammation plays a key role in atherosclerosis. The protective role of angiotensin 1-7 (Ang-(1-7)) in vascular pathologies suggested the therapeutic use of low MW, non-peptide Ang-(1-7) mimetics, such as AVE0991. The mechanisms underlying the vasoprotective effects of AVE0991, a Mas receptor agonist, remain to be explored. EXPERIMENTAL APPROACHWe investigated the effects of AVE0991 on the spontaneous atherosclerosis in apolipoprotein E (ApoE)À/À mice, in the context of vascular inflammation and plaque stability. KEY RESULTSAVE0991 has significant anti-atherosclerotic properties in ApoEÀ/À mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using the descending aorta of chow-fed ApoEÀ/À mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (PVAT) and adventitial infiltration with macrophages and T-cells precedes atherosclerotic plaque or the impairment of endothelium-dependent NO bioavailability (a measure of endothelial function). AVE0991 inhibited perivascular inflammation, by reducing chemokine expression in PVAT and through direct actions on monocytes/macrophages inhibiting their activation, characterized by production of IL-1β, TNF-α, CCL2 and CXCL10, and differentiation to M1 phenotype. Pretreatment with AVE0991 inhibited migration of THP-1 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in PVAT and in THP-1 cells in vitro, and the anti-inflammatory effects of AVE0991 were partly Mas dependent. CONCLUSIONS AND IMPLICATIONSThe selective Mas receptor agonist AVE0991 exhibited anti-atherosclerotic and anti-inflammatory actions, affecting monocyte/macrophage differentiation and recruitment to the perivascular space during early stages of atherosclerosis in ApoEÀ/À mice.

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“…Several independent reports suggest that deletion of ACE2 leads to vascular diseases (Thomas et al, ; Thatcher et al, ; Sahara et al, ; Rabelo et al, ). Furthermore, the MAS axis may be an interesting therapeutic target for multiple sclerosis and atherosclerosis (Hammer et al, ) and hypothermia (Souza et al, ). Activation of MAS could be an important target for the chronic hepatic and metabolic alterations during atherosclerosis (Silva et al, ).…”

Section: The Progress In Coupling Ang(1–7) Functions With Mas1 Receptorsmentioning

confidence: 99%

Significance of angiotensin 1–7 coupling with MAS1 receptor and other GPCRs to the renin‐angiotensin system: IUPHAR Review 22

Karnik

Singh

Tirupula

et al. 2017

British J Pharmacology

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This paper, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittees for the angiotensin receptors, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions, and their likely physiological roles in health and disease. More information on these receptor families can be found in the Concise Guide to PHARMACOLOGY Angiotensins are a group of hormonal peptides and include angiotensin II and angiotensin 1-7 produced by the renin angiotensin system. The biology, pharmacology and biochemistry of the receptors for angiotensins were extensively reviewed recently. In the review, the receptor nomenclature committee was not emphatic on designating MAS1 as the angiotensin 1-7 receptor on the basis of lack of classical G protein signalling and desensitization in response to angiotensin 1-7, as well as a lack of consensus on confirmatory ligand pharmacological analyses. A review of recent publications (2013-2016) on the rapidly progressing research on angiotensin 1-7 revealed that MAS1 and two additional receptors can function as 'angiotensin 1-7 receptors', and this deserves further consideration. In this review we have summarized the information on angiotensin 1-7 receptors and their crosstalk with classical angiotensin II receptors in the context of the functions of the renin angiotensin system. It was concluded that the receptors for angiotensin II and angiotensin 1-7 make up a sophisticated cross-regulated signalling network that modulates the endogenous protective and pathogenic facets of the renin angiotensin system.

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Role of the receptor Mas in macrophage-mediated inflammation in vivo

Cited by 65 publications

References 39 publications

Reduced disease severity following therapeutic treatment with angiotensin 1–7 in a mouse model of multiple sclerosis

Reduced disease severity following therapeutic treatment with angiotensin 1–7 in a mouse model of multiple sclerosis

Anti‐atherosclerotic effect of the angiotensin 1–7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis

Significance of angiotensin 1–7 coupling with MAS1 receptor and other GPCRs to the renin‐angiotensin system: IUPHAR Review 22

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