ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors

2020 ◽  
Vol 21 (9) ◽  
pp. 892-901 ◽  
Author(s):  
Ana Luiza Ataide Carneiro de Paula Gonzaga ◽  
Vitória Andrade Palmeira ◽  
Thomas Felipe Silva Ribeiro ◽  
Larissa Braga Costa ◽  
Karla Emília de Sá Rodrigues ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Pediatric Cancer ◽  
Pediatric Patients ◽  
Human Cancer ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Pediatric Tumors ◽  
Mas Receptor

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

Role of Angiotensin II AT1 Receptor Blockers in the Treatment of Arterial Hypertension

2003 ◽  
Vol 10 (6) ◽  
pp. 401-408 ◽  
Author(s):  
Freddy Contreras ◽  
Mar??a Antonia de la Parte ◽  
Julio Cabrera ◽  
Nestor Ospino ◽  
Zafar H. Israili ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Hypertension ◽  
At1 Receptor ◽  
Receptor Blockers ◽  
At1 Receptor Blockers

Controversies on neuroprotection therapy in non-arteritic anterior ischaemic optic neuropathy

2019 ◽  
Vol 104 (2) ◽  
pp. 153-156
Author(s):  
Sohan Singh Hayreh
Keyword(s):  
Clinical Trials ◽  
Ischaemic Stroke ◽  
Optic Neuropathy ◽  
Experimental Studies ◽  
Therapeutic Strategies ◽  
Ischaemic Optic Neuropathy ◽  
Pubmed Search ◽  
Anterior Ischaemic Optic Neuropathy ◽  
Study Designs

ObjectiveThere has long been a great interest in neuroprotection therapy for ischaemic stroke and various types of optic neuropathies. In view of that, I reviewed the literature on the role of neuroprotection for non-arteritic anterior ischaemic optic neuropathy (NA-AION).MethodsThe review is based on a PubMed search of literature about the use of neuroprotectors in stroke and optic neuropathies and about current clinical trials of RPh201 and QPI-1007 in NA-AION.ResultsSeveral neuroprotection agents for ischaemic stroke and various types of optic neuropathies have been evaluated extensively in experimental studies in animals and benefits claimed. However, translation of therapeutic strategies for neuroprotection from experimental research to humans has invariably been fraught with failure. Two currently ongoing studies dealing with neuroprotection by RPh201 and QPI-1007 in NA-AION may have limitations in their rationale and study designs.ConclusionsUnfortunately, in spite of all the experimental and clinical research on neuroprotection agents in NA-AION so far, we have no scientifically proven evidence of neuroprotection agents showing any benefit in the human clinical studies so far.

scholarly journals Renal Vascular Response to Angiotensin II Administration in Two Kidneys-One Clip Hypertensive Rats Treated with High Dose of Estradiol: The Role of Mas Receptor

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Samira Choopani ◽  
Mehdi Nematbakhsh
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Ovariectomized Rats ◽  
Ang Ii ◽  
Vascular Response ◽  
Hypertensive Rats ◽  
Vascular Responses ◽  
Mas Receptor ◽  
Renal Vascular

Backgrounds. High blood pressure is one of the most important causes of death around the world. The renin-angiotensin system (RAS) and estradiol are two important items that regulate arterial blood pressure in women. However, hypertension, RAS, and sex hormone estradiol may influence renal vascular responses. This study was designed to determine the role of Mas receptor (MasR) on renal vascular response to angiotensin II (Ang II) administration in two kidneys-one clip (2K1C) hypertensive rats treated with estradiol. Method. The ovariectomized rats were subjected to 2K1C or non-2K1C and simultaneously treated with estradiol (500 μg/kg/weekly) or placebo for a period of 4 weeks. Subsequently, under anesthesia, renal vascular responses to graded doses of Ang II administration with MasR blockade (A779) or its vehicle were determined. Results. A779 or its vehicle did not alter mean arterial pressure (MAP), renal perfusion pressure (RPP), and renal blood flow (RBF). However, in non-2K1C rats, Ang II infusion decreased RBF and increased renal vascular resistance (RVR) responses in a dose-related manner ( P treat < 0.0001 ). The greatest responses were found in ovariectomized estradiol-treated rats that received A779 ( P group < 0.05 ) in non-2K1C rats. Such findings were not detected in 2K1C hypertensive rats. For example, in estradiol-treated rats that received A779, at 1000 ng/kg/min of Ang II infusion, RBF reduced from 1.6 ± 0.2 to 0.89 ± 0.19  ml/min in non-2K1C rats, and it reduced from 1.6 ± 0.2 to 1.2 ± 0.2  ml/min in 2K1C rats. Conclusion. Hypertension induced by 2K1C may attenuate the role of A779 and estradiol in renal vascular responses to Ang II infusion. Perhaps, this response can be explained by the reduction of Ang II type 1 receptor (AT1R) expression in the 2K1C hypertensive rats.

Angiotensin ii and its role in regulation of heart tolerance to ischemia/reperfusion inhibitors and angiotensin ii at1-receptor antagonists

2019 ◽  
pp. 118-126
Author(s):  
Л.Н. Маслов ◽  
Н.В. Нарыжная ◽  
С.Ю. Цибульников ◽  
Н.С. Воронков ◽  
Ю.В. Бушов
Keyword(s):  
Angiotensin Ii ◽  
Infarct Size ◽  
Ace Inhibitors ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Convincing Evidence ◽  
No Production ◽  
Receptor Antagonists ◽  
At1 Receptor Antagonists

Цель обзора - анализ данных о роли ангиотензина II в регуляции толерантности сердца к действию ишемии/реперфузии, а также анализ данных о кардиопротекторных свойствах ингибиторов ангиотензинпревращающего фермента (АПФ) и антагонистов АТ1-рецептора ангиотензина II. Установлено, что ангиотензин II оказывает инфаркт-лимитирующий эффект, который, по одним данным, связан с активацией АТ1-рецептора, по другим - является следствием стимуляции АТ2-рецептора. Кроме того, ангиотензин способствовал улучшению сократимости сердца в реперфузионном периоде, эффект был связан с активацией AT1-рецептора. Установлено, что ангиотензин II и АТ1-рецептор участвуют в инфаркт-лимитирующем эффекте ишемического прекондиционирования. Экспериментальные данные о способности антагонистов AT1-рецептора влиять на размер инфаркта носят противоречивый характер: есть сообщения о способности этих антагонистов оказывать инфаркт-лимитирующий эффект, есть данные об отсутствии у них подобного эффекта. Экспериментальные данные свидетельствуют, что ингибиторы АПФ оказывают инфаркт-лимитирующий эффект, который связан с увеличением уровня брадикинина и усилением продукции NO. Нет убедительных данных о том, ингибиторы АПФ и антагонисты АТ1-рецептора оказывают инфаркт-лимитирующий эффект у пациентов с острым инфарктом миокарда. Однако ингибиторы АПФ и антагонисты АТ1-рецептора препятствуют постинфарктному ремоделированию сердца. The review analyzes reports on the role of angiotensin II in regulation of heart tolerance to ischemia/reperfusion and cardioprotective properties of angiotensin converting enzyme (ACE) inhibitors and angiotensin II AT1-receptor antagonists. Angiotensin II is known to have an infarct-limiting effect, which according to some reports is associated with activation of the AT1 receptor and according to other reports results from stimulation of the AT2 receptor. In addition, angiotensin improves heart contractility during reperfusion, which is associated with activation of the AT1 receptor. Angiotensin II and AT1 receptor are also involved in the infarct-reducing effect of ischemic preconditioning. Experimental data on the ability of AT1 receptor antagonists to influence the infarct size are inconsistent; one study showed that these antagonists can exert an infarct-limiting effect whereas there is some evidence against such effect. Experimental studies have suggested that ACE inhibitors can restrict the infarct size, which is associated with increased bradykinin level and NO production. There is no convincing evidence that ACE inhibitors and AT1 receptor antagonists can restrict the infarct size in patients with acute myocardial infarction. However, ACE inhibitors and AT1 receptor antagonists prevent post-infarction heart remodeling.

scholarly journals The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S188-S190
Author(s):  
Matthew R Weir ◽  
Chiming Wei
Keyword(s):  
Renal Function ◽  
Angiotensin Ii ◽  
Transforming Growth Factor ◽  
Experimental Studies ◽  
Chronic Allograft Nephropathy ◽  
Angiotensin Ii Receptor ◽  
Direct Stimulation ◽  
Converting Enzyme Inhibitors ◽  
Transplant Patients

Chronic allograft nephropathy is the most prevalent cause of graft dysfunction and failure. Its pathogenesis and treatment remains poorly defined. The calcineurin inhibitors, cyclosporine and tacrolimus, may play a role in the progressive loss of renal function in patients with chronic allograft nephropathy. This effect may be either related to the direct stimulation of profibrogenic cytokines such as transforming growth factor (TGF-β) or indirect mechanisms, through increases in blood pressure or alterations in either carbohydrate or lipid metabolism. Experimental studies have demonstrated that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) can attenuate cyclosporine-mediated increases in TGF-β production in renal tissue. Clinical studies have demonstrated that either cyclosporine or tacrolimus dose reduction may help reduce the rate of loss of renal function in patients with chronic allograft nephropathy. Moreover, other studies have demonstrated that a chronic reduction in the dose of cyclosporine in transplant patients can reduce serum TGF-β levels. Treatment with an ARB can normalise the plasma levels of TGF-β in renal transplant patients receiving cyclosporine. All these observations suggest that there may be a role of cyclosporine, and possibly tacrolimus, in worsening chronic allograft nephropathy through their effects on the renin-angiotensin-aldosterone system (RAAS) and TGF-β production.

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