Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study

Garg, Mayur; Burrell, Louise M.; Velkoska, Elena; Griggs, Karen; Angus, Peter W; Gibson, Peter R.; Lubel, John S

doi:10.1177/1470320314521086

Cited by 78 publications

(68 citation statements)

References 54 publications

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“…This protective effect was in part modulated through the expression/activity of several signaling molecules such as Ang II, p38 MAPK, ERK1/2, and Akt. It has been demonstrated that ACE2 is expressed in the epithelial, sub-mucosal and muscular layers of the colon in both humans and mice [33][34][35], and its expression levels are increased in the plasma of IBD patients [39]. We observed increased expression of ACE2 and MAS-1 R proteins in the colonic tissues of mice after DSS challenge (Fig 2), and higher Ang 1-7 levels in the inflamed colon homogenates ( Fig 1B).…”

Section: Discussionsupporting

confidence: 52%

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

et al. 2016

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BackgroundThere is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study.MethodsThe colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model.ResultsEnhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment.ConclusionOur results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.

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Section: Discussionsupporting

confidence: 52%

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

et al. 2016

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“…13 In vitro studies have shown that the latter form of ACE2 might act as a competitive interceptor of SARS-CoV-2 by preventing binding of the viral particle to the surface-bound, full-length ACE2. 14 Notably, the level of the soluble ACE2 is up-regulated in the peripheral blood of IBD patients, 15 raising the possibility that this isoform could contribute to limit SARS-CoV-2 infection.…”

mentioning

confidence: 99%

Are Patients with Inflammatory Bowel Disease at Increased Risk for Covid-19 Infection?

Monteleone

Ardizzone

2020

Journal of Crohn's and Colitis

185

178

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Crohn's disease [CD] and ulcerative colitis [UC], the main inflammatory bowel diseases [IBD] in humans, are chronic, immune-inflammatory diseases, the pathogenesis of which suggests a complex interaction between environmental factors and genetic susceptibility. These disabling conditions affect millions of individuals and, together with the drugs used to treat them, can put patients at risk of developing complications and other conditions. This is particularly relevant today, as coronavirus disease has rapidly spread from China to countries where IBD are more prevalent, and there is convincing evidence that Covid-19-mediated morbidity and mortality are higher in subjects with comorbidities. The primary objectives of this Viewpoint are to provide a focused overview of the factors and mechanisms by which the novel severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infects cells and to illustrate the link between such determinants and intestinal inflammation. We also provide clues about the reasons why the overall IBD population might have no increased risk of developing SARS-CoV-2 infection and highlight the potential of cytokine blockers, used to treat IBD patients, to prevent Covid-driven pneumonia.

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“…In addition, the absence of ACE2 in gut epithelial cells alters immunity and leads to increased inflammation (165). Both experimental animals (168) and humans (169) with acute intestinal inflammation have elevated plasma levels of ACE2 and angiotensin-(1-7). In animal models of acute intestinal inflammation, treatment with ARBs down regulates proinflammatory cytokines and reduces oxidative stress and epithelial apoptosis (170)(171)(172), and statins have similar effects (173)(174)(175).…”

Section: [Interestingly Influenza Viruses Naturally Cause Gastrointementioning

confidence: 99%

Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola

2016

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There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a "top down" approach to developing specific new drug treatments is unlikely to be effective. However, a "bottom up" approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.

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Upregulation of circulating components of the alternative renin-angiotensin system in inflammatory bowel disease: A pilot study

Cited by 78 publications

References 54 publications

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis

Are Patients with Inflammatory Bowel Disease at Increased Risk for Covid-19 Infection?

Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola

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