1,400,194 research outputs found
Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy
No full textMaternal endothelial dysfunction in preeclampsia is associated with increased soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antagonist of vascular endothelial growth factor and placental growth factor. Angiotensin II (Ang II) is a potent vasoconstrictor that increases concomitant with sFlt-1 during pregnancy. Therefore, we speculated that Ang II may promote the expression of sFlt-1 in pregnancy. Here we report that infusion of Ang II significantly increases circulating levels of sFlt-1 in pregnant mice, thereby demonstrating that Ang II is a regulator of sFlt-1 secretion in vivo. Furthermore, Ang II stimulated sFlt-1 production in a dose- and time-dependent manner from human villous explants and cultured trophoblasts but not from endothelial cells, suggesting that trophoblasts are the primary source of sFlt-1 during pregnancy. As expected, Ang II-induced sFlt-1 secretion resulted in the inhibition of endothelial cell migration and in vitro tube formation. In vitro and in vivo studies with losartan, small interfering RNA specific for calcineurin and FK506 demonstrated that Ang II-mediated sFlt-1 release was via Ang II type 1 receptor activation and calcineurin signaling, respectively. These findings reveal a previously unrecognized regulatory role for Ang II on sFlt-1 expression in murine and human pregnancy and suggest that elevated sFlt-1 levels in preeclampsia may be caused by a dysregulation of the local renin/angiotensin system
Ang-II induces ACE translocation to the nucleus.
No full text(A) Internalization of AT1 and ACE in the presence of 4 nM 3H-Ang-II. Data are shown as mean from three independent experiments, each performed in duplicate. (B) CHO-ACE and CHO-AT1 cells present the same relative protein level of each respective receptor. (Values are mean ± S.E.M, *p1 cells after 30 seconds of Ang-II stimulation. DAPI (blue) and Wheat Germ Agglutinin (red), scale bar = 10 μm. On the right, quantification of internalized Ang-II-FITC is presented. Values are mean ± S.E.M, *p<0.05, n = 6. (D) Representative confocal images of unstimulated CHO-ACE and CHO-AT1 cells, labeled for DAPI and WGA. (E) Immunolocalization of ACE after stimulation with Ang-II (1μM), for the indicated times. ACE is shown in green, actin filaments in red, and nucleus in blue (DAPI). Right panel represents a 3D reconstruction of CHO-ACE cell after 15 minutes of incubation with Ang-II (1μM). Scale bar = 10μm. (F) Western blotting of nuclear and non-nuclear protein fractions from CHO-ACE cells, before (control) and after Ang-II (1 μM) stimulation for the indicated times. Histone-3 and GAPDH were used to shown the purification of nuclear and non-nuclear protein fractions, respectively. (G) Densitometry analysis of the western blot. Values are mean ± S.E.M., n = 3 (*** p<0.01).</p
Ang-2 over-expression impairs islet function but protects from cytokine treatment in isolated islets.
No full textIsolated islets from RIP-rtTA;tet-O-Ang-2 (Ang2-rtTA) and RIP-rtTA control (rtTA) mice were cultured for 3 days in presence of 10 μg/ml doxycycline to achieve Ang-2 overexpression. Mouse or human islets were cultured in 11.1 (mouse) or 5.5 mM glucose (human) or treated with diabetic conditions of 22.2 mM glucose + 0.5mM palmitic acid or mixture of cytokines: 2 ng/mL IL-1β, 1000 U/ml IFN-ɣ and TNF-α (cyto). (A) Western blot from treated mouse islets shows Ang-2 overexpression in islets by myc-Ang-2. (B) GSIS is shown by the stimulatory index assessed by 16.7/2.8 mM glucose stimulation and normalized to control. (C,D) Treated mouse islets fixed post-GSIS and apoptotic cells detected by double staining for TUNEL and insulin. Representative images from different treatments. (E,F) qPCR analysis for CD31 (E) and ICAM (F) from mouse islets overexpressing Ang-2. (G,H) Representative western blots (upper panel) and densitometric analyses of proteins (lower panels) showing myc-Ang-2, ICAM-1, cleaved caspase 3 and actin/tubulin as housekeeping control, in human islets overexpressing Ang-2 by Ad-Ang-2 or control Ad-GFP (G; MOI = 50) or treated with 100 nM Tie-2 inhibitor for 72h (H). Data are means +/-SE from 3–5 independent experiments from 3–5 different organ donors (human islets) or 3–5 independent mouse islet isolations. *p<0.05, treated vs. 11.1 mM glucose control, #p<0.05, Ang2-rtTA vs. rtTA.</p
Ang-(1-7)/ MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma - Fig 6
No full textRepresentative low-magnification light photomicrographs display H&E staining (Fig 6(a)), Masson's Trichrome staining (Fig 6(b)) and PAS stain Fig 6(c)) of whole lung samples from PBS-challenged/ vehicle treated (n = 6) (PBS), OVA-challenged/ vehicle treated (n = 6) (OVA), OVA-challenged/Ang-(1–7) treated (0.3 mg/kg; n = 6) (Ang-1–7), OVA-challenged/Ang-(1–7) and A779 treated (0.3 mg/kg; n = 6 and 1mg/kg; n = 5; respectively) (Ang-1–7 + A779), OVA-challenged/dexamethasone treated (1 mg/kg; n = 6) (DEX). OVA-challenged/vehicle treated mice showed marked and significant peribronchial and perivascular inflammatory cell infiltrations (a) peribronchial and perivascular fibrosis (b) and bronchial mucus production and goblet cell hyper/metaplasia (c) compared with PBS-challenged vehicle treated mice. Treatment with Ang-(1–7) resulted in a significant reduction in the peribronchial and perivascular dark-staining inflammatory cell infiltration (a), peribronchial and perivascular fibrosis (b) and bronchial mucus production and goblet cell hyper/metaplasia (c) compared to the OVA – challenged mice and was comparable to PBS-challenged and OVA-challenged/dexamethasone treated mice. Effect of Ang-(1–7) (0.3 mg/kg) on inflammation severity score is shown in Fig 6(d). Data are expressed as mean ± SEM (n = 5–6). *P #P P < 0.05 versus time-matched Ang-(1–7)-treated ovalbumin-challenged mice.</p
Ang-II stimulates proliferation in melanoma cells.
No full text(A) Real-Time PCR analysis for expression of ACE in melan-a and TM-5 cells. (B) ACE activity measured by cleavage of Abz-FRK(Dnp)P-OH in melan-a and TM-5 cells. For A and B, mean ± S.E.M, n = 6 (**p<0.01). (C-D) BrDU uptake assay 24 hours after stimulation with Ang-II (1μM) in the presence of lisinopril (1μM), showing inhibition of cell proliferation in TM-5 cells (D) but not in melan-a cells (C). Mean ± S.E.M., n = 6. (*p<0.05).</p
Ang, Jeffery
No full textCapt. Jeffery Ang, a commercial airline pilot, started his flying career at the age of 19 with the Republic of Singapore Air Force. As a military pilot on the C130 Hercules aircraft, he had flown and participated in numerous Humanitarian Assistance and Disaster Relief Operations, United Nations Peacekeeping Missions, and Air Defense Exercises both locally in Singapore and overseas.
After 12 years of military flying, he joined SIA in 1999, attained his commandership on the Boeing 777 wide body airliner in May 2007, and flew that aircraft until Sept 2018. Currently, he is an aircraft commander on the Boeing 787-10, commonly known as the “Dreamliner”.
With more than 3 decades of flying, he has acquired experiences as a Line Instructor Pilot on the B777, a Supervisory Captain (Instructor) on the B787, a Peer Supporter of the Pilot’s Advisory Group (PAG), and as Branch Chairman of the Air Line Pilots Association of Singapore (ALPA-S).
Academically, he holds the Bachelor of Aviation Management from Massey University and attended the Counselling Skills and Practice (Introductory) with the Social Service Institute. Additionally, he is also an Industry Mentor to students from Ngee Ann Polytechnic and undergraduates from Nanyang Technological University.
Capt. Jeffery is blissfully married with two adult sons.https://commons.erau.edu/aviasian-bios-2021/1003/thumbnail.jp
Ang-(1-7)/ MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma.
No full textThe angiotensin-(1-7) [Ang-(1-7)]/MAS1 receptor signaling axis is a key endogenous anti-inflammatory signaling pathway. However, the mechanisms by which its mediates the anti-inflammatory effects are not completely understood. Using an allergic murine model of asthma, we investigated whether Ang-1(1-7)/MAS1 receptor axis a): inhibits allergic inflammation via modulation of Src-dependent transactivation of the epidermal growth factor receptor (EGFR) and downstream signaling effectors such as ERK1/2, and b): directly inhibits neutrophil and/or eosinophil chemotaxis ex vivo. Ovalbumin (OVA)-induced allergic inflammation resulted in increased phosphorylation of Src kinase, EGFR, and ERK1/2. In addition, OVA challenge increased airway cellular influx, perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyperresponsiveness (AHR). Treatment with Ang-(1-7) inhibited phosphorylation of Src kinase, EGFR, ERK1/2, the cellular and histopathological changes and AHR. Ang-(1-7) treatment also inhibited neutrophil and eosinophil chemotaxis ex vivo. These changes were reversed following pre-treatment with A779. These data show that the anti-inflammatory actions of Ang-(1-7)/ MAS1 receptor axis are mediated, at least in part, via inhibition of Src-dependent transactivation of EGFR and downstream signaling molecules such as ERK1/2. This study therefore shows that inhibition of the Src/EGRF/ERK1/2 dependent signaling pathway is one of the mechanisms by which the Ang-(1-7)/ MAS1 receptor axis mediates it anti-inflammatory effects in diseases such as asthma.This study was supported by Kuwait University Research Sector - grant # PT01/12. Parts of this work were supported by the research grant # SRUL02/12 to the Research Unit for Genomics, Proteomics and Cellomics Studies through the Research Core Facility. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Ang-(1-7)/ MAS1 receptor axis inhibits allergic airway inflammation via blockade of Src-mediated EGFR transactivation in a murine model of asthma - Fig 8
No full textEffect of Ang (1–7) treatment on (a) neutrophil and (b) eosinophil chemotaxis towards BALF taken from either vehicle- or OVA-treated mice. Treatment with Ang-(1–7) inhibited both neutrophil and eosinophil migration. Treatment with A779 inhibited the eosinophil migration. Data are expressed as mean ± SEM (n = 5–8). *P versus time-matched PBS-challenged mice. #Pversus time-matched OVA-challenged mice.</p
Identification of ANG-binding DNA fragments.
No full text<p>(<b>A</b>) Schematic illustration of ChIP screen of ANG-binding DNA. (<b>B</b>) Sonicated chromatin samples from HeLa cells were immunoprecipitated overnight with ANG antibody or IgG and applied to Western blot analysis. Data showed specific enrichment of ANG in the antibody group.</p
ANG-19-10-475-R1_Suppl_App - Egg Consumption and Coronary Artery Disease: A Nice Knockdown Argument
No full textANG-19-10-475-R1_Suppl_App for Egg Consumption and Coronary Artery Disease: A Nice Knockdown Argument by Hisato Takagi, Yosuke Hari, Kouki Nakashima, Toshiki Kuno, Tomo Ando and for The ALICE (All-Literature Investigation of Cardiovascular Evidence) Group in Angiology</p
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