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Hang Nguyen, Bruce D Uhal
Recent work from this laboratory showed that endoplasmic reticulum (ER) stress-induced apoptosis of alveolar epithelial cells (AECs) is regulated by the autocrine angiotensin (ANG)II/ANG1-7 system. The proteasome inhibitor MG132 or surfactant protein C (SP-C) BRICHOS domain mutation G100S induced apoptosis in human AECs by activating the pro-apoptotic cathepsin D and reducing anti-apoptotic angiotensin converting enzyme-2 (ACE-2). This study tested the hypothesis that ER stress-induced apoptosis of human AECs might be mediated by influence of the unfolded protein response (UPR) on the autocrine ANGII/ANG1-7 system...
September 16, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
R Hmazzou, A Flahault, Y Marc, C Llorens-Cortes
OBJECTIVE: In the brain, angiotensin III (AngIII) generated from angiotensin II (AngII) by aminopeptidase A (APA) exerts a tonic stimulatory action on the control of blood pressure (BP) in hypertensive rats. Inhibition of brain APA by RB150 (also known as QGC001), an orally active prodrug of the specific and selective APA inhibitor EC33, blocks brain AngIII formation and normalizes BP in hypertensive rats. Thus, RB150 has emerged as the prototype of a new class of centrally-acting antihypertensive agents and is currently evaluated in a phase II clinical trial in hypertensive patients...
September 2016: Journal of Hypertension
Maryam Maleki, Mehdi Nematbakhsh
Background. Angiotensin 1-7 (Ang1-7) plays an important role in renal circulation. Hemorrhagic shock (HS) may cause kidney circulation disturbance, and this study was designed to investigate the renal blood flow (RBF) response to Ang1-7 after HS. Methods. 27 male Wistar rats were subjected to blood withdrawal to reduce mean arterial pressure (MAP) to 45 mmHg for 45 min. The animals were treated with saline (group 1), Ang1-7 (300 ng·kg(-1) min(-1)), Ang1-7 in hypertonic sodium chloride 7.5% (group 3), and hypertonic solution alone (group 4)...
2016: International Journal of Vascular Medicine
Maitham A Khajah, Maryam M Fateel, Kethireddy V Ananthalakshmi, Yunus A Luqmani
BACKGROUND: There 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. METHODS: The colonic expression/activity profile of ACE2, Ang 1-7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence...
2016: PloS One
Indiwari Gopallawa, Bruce D Uhal
Earlier work from this laboratory showed that autocrine generation of angiotensin II and c-Jun-NH2-terminal kinase phosphorylation (p-JNK) are both required events in alveolar epithelial cell (AEC) apoptosis. Although earlier data showed that angiotensin-(1-7) [ANG-(1-7)] protects against AEC apoptosis, the pathways by which ANG-(1-7)/mas activation prevent JNK phosphorylation and apoptosis are poorly understood. Therefore, in the current study, it was theorized that ANG-(1-7) activates a mitogen-activated protein kinase phosphatase (MKP) and thereby reduces JNK phosphorylation to inhibit apoptosis and promote cell survival...
February 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Fleur Bossi, Stella Bernardi, Daniele De Nardo, Alessandra Bramante, Riccardo Candido, Renzo Carretta, Fabio Fischetti, Bruno Fabris
OBJECTIVE: Recent studies have demonstrated that Ang1-7 has anti-inflammatory effects. Since the formation of Ang1-7 is significantly altered in the setting of diabetes, here we aimed to evaluate whether Ang1-7 infusion could ameliorate diabetes-induced leukocyte recruitment. METHODS: Wild-type male Wistar rats were randomly allocated to the following groups: control + saline, control + Ang1-7, diabetes + saline, diabetes + Ang1-7. Diabetes was induced by streptozotocin...
January 2016: Atherosclerosis
Aghdas Dehghani, Shadan Saberi, Mehdi Nematbakhsh
Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg(-1) min(-1)) were determined...
2015: Advances in Pharmacological Sciences
Anuradha Pandey, Santosh Kumar Goru, Almesh Kadakol, Vajir Malek, Anil Bhanudas Gaikwad
Angiotensin II (Ang II) acts through Angiotensin Converting Enzyme (ACE)/Ang II type 1 receptor (AT1R) axis to promote renal failure whereas the Ang II type 2 receptor (AT2R)/Angiotensin Converting Enzyme 2 (ACE2)/Ang1-7/Mas axis constitutes the protective arm of Renin Angiotensin System (RAS). Though Ang II has been known to activate the Nuclear Factor-κB (NF-κB) signalling pathway through different receptor subtype(s) in different tissues under various diseases, the subtype orchestrating this stimulation in type 2 diabetic kidney remains elusive...
November 2015: Biochimie
Pengjun Zhao, Fen Li, Wei Gao, Jing Wang, Lijun Fu, Yiwei Chen, Meirong Huang
Angiotensin1-7 (Ang1-7) is a biologically active member of the renin-angiotensin system, which has been reported to exhibit protective effect in myocardial ischemia reperfusion-induced injury. However, the molecular basis of this effect is not well understood. It has been proposed that oxidative stress-induced cardiomyocyte apoptosis is a major consequence of hypoxia/reoxygenation (H/R) injury. This study investigates the protective effect of Ang1-7 against H/R-induced oxidative stress in rat H9C2 cells. Our results showed that Ang1-7 (80nM) treatment significantly protected cells from H/R-induced oxidative injury via improving cell viability and reducing cell apoptosis...
October 2015: Acta Histochemica
Xia Li, You-dong Hu, Ying Chen, Hua-lan Zhou, Feng-lin Zhang, Dian-xuan Guo, Qing-na Zhao
We have evaluated the safety and efficacy of intracoronary human umbilical cord-derived mesenchymal stem cell (hUCMSC) treatment for very old patients with coronary chronic total occlusion. hUCMSCs could improve in the degree of ischemic myocardium, decrease in the infarct size and rise in left ventricular ejection fraction, but the involved mechanisms remain to be fully identified. We analyzed levels of circulating leukocytes, highsensitivity C-reactive protein (hs-CRP), interleukins (ILs), tumor necrosis factor-a (TNF-a), soluble tumor necrosis factor receptor-1 (sTNFR-1), soluble tumor necrosis factor receptor-2 (sTNFR-2), NT-proBNP, BNP, angiotensin 1-7 (Ang1-7), angiotensin II (Ang II) and aldosterone (Ald) in patients with hUCMSC therapy at baseline, 12, and 24 months...
2015: Current Pharmaceutical Design
Indiwari Gopallawa, Bruce D Uhal
An established body of recent literature has demonstrated potent inhibitory effects of the angiotensin converting enzyme-2 (ACE-2)/ANG1-7/ Mas axis on acute lung injury and lung fibrogenesis. One of the mechanisms of this inhibition is the enzymatic action of ACE-2 to degrade its main substrate angiotensin (ANG) II, thereby reducing the injurious and profibrotic activities of this octapeptide. Another, potentially more important mechanism is the production by ACE-2 of the heptapeptide ANG1-7, which inhibits the actions of ANGII through its own receptor Mas, the product of the oncogene of the same name...
January 1, 2014: Current Topics in Pharmacology
Sylvie Rodrigues-Ferreira, Clara Nahmias
G-protein coupled receptors (GPCRs) constitute the largest family of membrane receptors, with high potential for drug discovery. These receptors can be activated by a panel of different ligands including ions, hormones, small molecules, and vasoactive peptides. Among those, angiotensins [angiotensin II (AngII) and angiotensin 1-7] are the major biologically active products of the classical and alternative renin-angiotensin system (RAS). These peptides bind and activate three different subtypes of GPCRs, namely AT1, AT2, and Mas receptors, to regulate cardiovascular functions...
2015: Frontiers in Pharmacology
Daniel Clayton, Iresha Hanchapola, Walter G Thomas, Robert E Widdop, Alexander I Smith, Patrick Perlmutter, Marie-Isabel Aguilar
Angiotensin converting enzyme 2 (ACE2) is a zinc carboxypeptidase involved in the renin-angiotensin system (RAS) and inactivates the potent vasopressive peptide angiotensin II (Ang II) by removing the C-terminal phenylalanine residue to yield Ang1-7. This conversion inactivates the vasoconstrictive action of Ang II and yields a peptide that acts as a vasodilatory molecule at the Mas receptor and potentially other receptors. Given the growing complexity of RAS and level of cross-talk between ligands and their corresponding enzymes and receptors, the design of molecules with selectivity for the major RAS binding partners to control cardiovascular tone is an on-going challenge...
2015: Frontiers in Pharmacology
A Mansoori, S Oryan, M Nematbakhsh
Sexual differences in blood pressure are associated with angiotensin 1-7 (Ang1-7) and its receptor and enzyme function targeting. Blockade of angiotensin II (AngII) receptors type 1 and 2 (AT1R and AT2R) inhibits some actions of Ang1-7. We described the role of Ang1-7 receptor (MasR) antagonist (A779) on kidney hemodynamics when AT1R and AT2R are blocked with losartan and PD123319. In anaesthetized male and female rats after blockade of both AT1R and AT2R, the renal perfusion pressure (RPP) was controlled in two levels of 80 and 100 mmHg via an adjustable clamp placed around the aorta above the level of the renal arteries...
October 2014: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Pamella Huey Mei Wang, Maria Claudina Andrade, Beata Marie Redublo Quinto, Giovana Di Marco, Renato Arruda Mortara, Carlos P Vio, Dulce Elena Casarini
Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE)...
January 2015: International Journal of Biological Macromolecules
Jiao-Lin Zheng, Guang-Ze Li, Shu-Zhen Chen, Jin-Ju Wang, James E Olson, Hui-Jing Xia, Eric Lazartigues, Yu-Lan Zhu, Yan-Fang Chen
BACKGROUND: The angiotensin (Ang) converting enzyme 2 (ACE2)/Ang-(1-7)/Mas receptor pathway is an important component of the renin-angiotensin system and has been suggested to exert beneficial effects in ischemic stroke. AIMS: This study explored whether the ACE2/Ang-(1-7)/Mas pathway has a protective effect on cerebral ischemic injury and whether this effect is affected by age. METHODS: We used three-month and eight-month transgenic mice with neural over-expression of ACE2 (SA) and their age-matched nontransgenic (NT) controls...
May 2014: CNS Neuroscience & Therapeutics
Weixin Meng, Wenyuan Zhao, Tieqiang Zhao, Chang Liu, Yuanjian Chen, Hongyu Liu, Yao Sun
BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin (Ang) II to generate Ang1-7, which mediates cellular actions through Mas receptors (MasR). Hypertension is accompanied by high or low circulating AngII levels and cardiac/renal injury. The purpose of this study is to explore (i) whether circulating AngII affects ACE2/MasR expressions in the hypertensive heart and kidney; and (ii) whether Ang1-7 regulates cardiac repair/remodeling responses through MasR during hypertension...
June 2014: American Journal of Hypertension
Ying Meng, Chang-hui Yu, Shao-xi Cai, Xu Li
OBJECTIVE: To explore the anti-fibrotic effects of angiotensin (Ang) 1-7 on bleomycin (BLM) -induced pulmonary fibrosis in rats. METHODS: Eighteen Wistar male rats were randomly divided into 3 groups, including control group (intratracheal instillation with physiological saline and subcutaneous micro-pump with bi-distilled water at the rate of 0.29 µl/h), BLM group (intratracheal instillation with bleomycin and subcutaneous micro-pump with bi-distilled water at the same rate) and BLM+Ang1-7 group (intratracheal instillation with bleomycin and subcutaneous micro-pump with Ang1-7 at a dose of 25 µg·kg(-1) · h(-1) at the same rate)...
May 28, 2013: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jun Mori, Liyan Zhang, Gavin Y Oudit, Gary D Lopaschuk
The renin-angiotensin system (RAS) plays a key pathogenic role in heart failure. The adverse effects of angiotensin II (Ang II), a major player of the RAS, contributes to the development of heart failure. Heart failure is accompanied by significant perturbations in cardiac energy metabolism that can both decrease cardiac energy supply and decrease cardiac efficiency. Recent evidence suggests that Ang II might be involved in these perturbations in cardiac energy metabolism. Furthermore, new components of the RAS, such as angiotensin converting enzyme 2 and Ang1-7, have been reported to exert beneficial effects on cardiac energy metabolism...
October 2013: Journal of Molecular and Cellular Cardiology
Manuel Haschke, Manfred Schuster, Marko Poglitsch, Hans Loibner, Marc Salzberg, Marcel Bruggisser, Joseph Penninger, Stephan Krähenbühl
BACKGROUND AND OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II (Ang1-8) to angiotensin 1-7 (Ang1-7), a functional antagonist of Ang1-8, with vasodilatory, antiproliferative, antiangiogenic, and anti-inflammatory properties. In conditions with an unbalanced renin-angiotensin-aldosterone system with elevated Ang1-8, administration of ACE2 has shown promising effects in a variety of animal models. Enhancing ACE2 activity by exogenous administration of ACE2 might also be beneficial in human diseases with pathologically elevated Ang1-8...
September 2013: Clinical Pharmacokinetics
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