<scp>ACE2</scp>, angiotensin‐(1‐7) and <scp>M</scp>as receptor axis in inflammation and fibrosis

Silva, Ana Cristina Simões e; Silveira, Kátia D.; Ferreira, AJ; Teixeira, M.M.

doi:10.1111/bph.12159

Cited by 494 publications

(423 citation statements)

References 175 publications

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“…In order to evaluate the effects produced by Ang-(1-7)-Mas receptor axis, other studies have used A-779 (Ferreira et al 2011;Simões & Silva et al 2013). In the present study, the acute administration of A-779 in control rats did not produce any effect when compared to saline administration.…”

Section: R a F Tmentioning

confidence: 99%

Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein

Dartora¹,

Irigoyen

Casali

et al. 2017

Can. J. Physiol. Pharmacol.

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Keyword:renin-angiotensin system, angiotensin-(1-7), A-779, autonomic nervous system, blood pressure https://mc06.manuscriptcentral.com/cjpp-pubs However, it has yet to be determined how cardiovascular autonomic modulation may be affected by chronic and acute elevation of Ang-(1-7). Hemodynamics and cardiovascular autonomic profile were evaluated in male Sprague-Dawley (SD) and transgenic rats (TGR) overexpressing Ang-(1-7) [TGR(A1-7)3292].Blood pressure (BP) was directly measured while cardiovascular autonomic modulation was evaluated by spectral analysis. TGR received A-779 or vehicle and SD rats received Ang-(1-7) or vehicle and were monitored for 5 hours after i.v. administration. In another set of experiments with TGR, A-779 was infused for 7 days using osmotic mini pumps. Although at baseline no differences were observed, acute administration of A-779 in TGR produced a marked long lasting increase in BP accompannied by increased BP variability (BPV) and sympathetic modulation to the vessels. Likewise, chronic administration of A-779 with osmotic mini pumps in TGR increased heart rate, sympathovagal balance, BPV and sympathetic modulation to the vessels. Administration of Ang-(1-7) to SD rats increased HRV values in 88% accompannied by 8% of vagal modulation increase and 18% of mean BP reduction. These results show that both acute and chronic alteration in the Ang-(1-7)-Mas receptor axis may lead to important changes in the autonomic control of circulation, impacting either sympathetic and/or parasympathetic systems.Keywords: Renin-angiotensin system, angiotensin-(1-7), A-779, blood pressure, autonomic nervous system, heart rate variability, spectral analysis. IntroductionThe renin-angiotensin system (RAS) is a key regulatory mechanism of the renal, cardiovascular and autonomic nervous systems (Baltatu et al. 2011).The discovery and characterization of Ang-(1-7) and its receptor Mas is one of the most significant recent changes in the understanding of the system, particularly the mechanisms linked to this axis, which counterbalance most of the deleterious effects of Ang II (Ferrario 2011; Oudit et al. 2003; Reudelhuber 2011;Santos et al. 2008;Santos and Andrade 2014).The beneficial biological effects of Ang-(1-7) described in the last two decades include vasodilation, antiproliferative effects on smooth muscle cells (Freeman et al. 1996), increased baroreflex sensitivity (Campagnole-Santos et al. 1992; Oliveira et al. 1996), decreased oxidative stress (Fraga-Silva et al. 2008), and improved glucose and lipid metabolism . In a recent study conducted by our group, using a rat model of genetic hypertension, we observed a decrease in blood pressure and an improvement in autonomic modulation of the cardiovascular system after chronic treatment with an oral formulation of Ang-(1-7) (Bertagnolli et al. 2014).The autonomic nervous system seems to be a key mechanism in the cardiovascular responses to Ang-(1-7), since intracerebroventricular injection or microinjections of the peptide in the nucleus of the sol...

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Section: R a F Tmentioning

confidence: 99%

Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein

Dartora¹,

Irigoyen

Casali

et al. 2017

Can. J. Physiol. Pharmacol.

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“…ACE2 cleaves Ang II to yield Ang (1)(2)(3)(4)(5)(6)(7) and is the rate-limiting enzyme in this conversion. 18 We speculate that ACE2 is the key component that negatively regulates leptin release; further experiments are necessary to confirm this hypothesis. Because our animal experiments were based on MetS rats, and the basis of MetS is insulin resistance, we sought to explore the effect of changes in ACE2 expression on leptin level by establishing an insulin-resistant (IR) VA model and using ACE2 siRNA and lentiviral-ACE2 (lenti-ACE2) to silence and overexpress ACE2, respectively.…”

Section: Ang(1-7) Inhibits Leptin Release From Vas By Activating Thementioning

confidence: 78%

Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue

Liu

et al. 2016

Hypertension

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Abstract-Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogenactivated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy. (Hypertension. 2016;68:478-490.

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“…They are participating in the progression of disease, or contrary, in mechanisms that protect from tissue injury [12]. These components include the (pro) renin receptor [15,16], renin-independent mechanisms of Ang peptide generation from Ang-(1-12) [17,18], intracellular RAS [19], previously mentioned ACE2/Ang-(1-7)/Mas receptor pathway [20] and they all may possess therapeutic potential.…”

Section: Tissue and Intracellular Rasmentioning

confidence: 99%

Involvement of the Renin‐Angiotensin System in Atherosclerosis

Kolaković¹,

Živković²,

Stanković³

2017

Renin-Angiotensin System - Past, Present and Future

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The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

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ACE2, angiotensin‐(1‐7) and Mas receptor axis in inflammation and fibrosis

Cited by 494 publications

References 175 publications

Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein

Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein

Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue

Involvement of the Renin‐Angiotensin System in Atherosclerosis

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