2,967 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
Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes
No full textInflammation is a common cause of cardiac arrhythmia. Angiotensin II (Ang II) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang II on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang II activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Ang II decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-β1 induction. Ang II induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang II-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-β signalling pathways. Ang II concentration, along with TGF-β1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang II induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation. © 2017 The Author(s)
FIN219, an auxin-regulated gene, defines a genetic link between phytochrome A and the downstream regulator COP1 in light control of Arabidopsis development
No full textPerformances of the HL (Hyperloop) transport system
No full textThis paper deals with an analysis of performances of the HL (Hyperloop) transport system considered as an advanced transport alternative to the existing APT (Air Passenger Transport) and HSR (High Speed Rail) systems. The considered performances are operational, financial, social and environmental. The operational performance include capacity and quality of service provided to the system’s users-passengers with attributes such as door-to-door travel time consisting of the access and egress time, schedule delay, in-vehicle time, and interchange time. The economic performances embrace the costs and revenues of operating the system. The costs include that for infrastructure, vehicles, traffic management facilities and equipment, and employees. The revenues embrace earnings from pricing users/passengers. The environmental performances include energy consumption and related emissions of GHGs (Green House Gases), and land use. The social performances are considered to be noise and safety. The analytical models of indicators of these performances are developed and applied to the scenario of operating the HL system on the short- to medium-haul travel distances/routes. These are then compared to the corresponding performances of the HSR and APT. This comparison has shown that the HL system may possess some advantages but also disadvantages regarding particular performances.Transport and PlanningOLD Urban and Regional Developmen
Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes
No full textAbstractInflammation is a common cause of cardiac arrhythmia. Angiotensin ІІ (Ang ІІ) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang ІІ on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang ІІ activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α). Ang ІІ decreased oxygen consumption rate, which resulted in reactive oxygen species (ROS) generation and inhibition of ROS blocked Ang II-mediated JNK phosphorylation and TGF-β1 induction. Ang ІІ induced the expression of its specific receptor, AT1R. Ang II-induced intracellular calcium production associated with Ang ІІ-mediated signalling pathways. In addition, the generated ROS and calcium stimulated AMPK phosphorylation. Inhibiting AMPK blocked Ang II-mediated JNK and TGF-β signalling pathways. Ang ІІ concentration, along with TGF-β1 and tumor necrosis factor-α levels, was slightly increased in plasma of patients with atrial fibrillation. Taken together, these results suggest that Ang ІІ induces inflammation mechanisms through an AMPK-related signalling pathway. Our results provide new molecular targets for the development of therapeutics for inflammation-related conditions, such as atrial fibrillation.</jats:p
Angiotensin (ang) 1-7 inhibits ang II-induced atrial fibrosis through regulating the interaction of proto-oncogene tyrosine-protein kinase Src (c-Src) and Src homology region 2 domain-containing phosphatase-1 (SHP-1))
No full textTo verify whether Ang-(1-7) produces an antagonistic effect on Ang II-mediated atrial remodeling. Ang II–induced HL-1 cell model and a rat model of Ang II–induced atrial remodeling were constructed and intervened with Ang II Ang-(1-7), AngII +Ang-(1-7), Ang II+ c-Src specific inhibitor (SU6656), and Ang II + Ang-(1-7) + SSG (SHP-1/2 specific inhibitor, stibogluconate), respectively. The systolic blood pressure of the rat caudal artery was detected. And trial fibrosis was detected by Picrosirius red staining and Masson’s trichrome staining. Expressions of transforming growth factor-β (TGF-β), tissue inhibitor of metalloproteinases 1 (TIMP1), Matrix metalloproteinase 2 (MMP-2), connective tissue growth factor (CTGF), galectin-3, α-smooth muscle actin (α-SMA), and collagen I/III were subjected to qPCR and western blot. Furthermore, SHP-1 binding to c-Src was verified by co-immunoprecipitation (Co-IP). Results showed that the expressions of TGF-β, TIMP1, MMP-2, CTGF, α-SMA, galectin-3, and collagen I were increased markedly in the Ang II intervention group, and the expressions of p-ERK1/2, p-Akt, and p-p38MAPK were also increased dramatically. Ang-(1-7) or SU6656 addition could inhibit the action of Ang II factor, thereby minimizing the expressions of the previously described genes and proteins. Simultaneously, SSG supplement reversed the antagonistic effect of Ang-(1-7) on Ang II, and the latter elevated the blood pressure and induced atrial fibrosis in rats. Ang-(1-7) could reverse the changes related to Ang II–induced atrial fibrosis in rats. In conclusion, Ang-(1-7) antagonized Ang II–induced atrial remodeling by regulating SHP-1 and c-Src, thereby affecting the MAPKs/Akt signaling pathway.</p
Analysis and modelling of performances of the HL (Hyperloop) transport system
No full textIntroduction: Hyperloop (HL) is presented as an efficient alternative of HSR (High Speed Rail) and APT (Air Passenger Transport) systems for long-distance passenger transport. This paper explores the performances of HL and compares these performances to HSR and APT. Methods: The following performances of the HL system are analytically modeled and compared to HSR and APT: (i) operational performance; (ii) financial performance; (iii) social/environmental performance. Results: The main operational result is that the capacity of HL is low which implies a low utilization of the infrastructure. Because the infrastructure costs dominate the total costs, the costs per passenger km are high compared to those for HSR and APT. The HL performs very well regarding the social/environmental aspects because of low energy use, no GHG emissions and hardly any noise. The safety performance needs further consideration. Conclusions: The HL system is promising for relieving the environmental pressure of long-distance travelling, but has disadvantages regarding the operational and financial performances.Transport and PlanningOLD Urban and Regional Developmen
Reciprocal changes in renal ACE/ANG II and ACE2/ANG 1-7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats
No full textPrieto MC, Gonzalez-Villalobos RA, Botros FT, Martin VL, Pagan J, Satou R, Lara LS, Feng Y, Fernandes FB, Kobori H, Casarini DE, Navar LG. Reciprocal changes in renal ACE/ANG II and ACE2/ANG 1-7 are associated with enhanced collecting duct renin in Goldblatt hypertensive rats. Am J Physiol Renal Physiol 300: F749-F755, 2011. First published January 5, 2011; doi:10.1152/ajprenal.00383.2009.-Alterations in the balance between ANG II/ACE and ANG 1-7/ACE2 in ANG II-dependent hypertension could reduce the generation of ANG 1-7 and contribute further to increased intrarenal ANG II. Upregulation of collecting duct (CD) renin may lead to increased ANG II formation during ANG II-dependent hypertension, thus contributing to this imbalance. We measured ANG I, ANG II, and ANG 1-7 contents, angiotensin-converting enzyme (ACE) and ACE2 gene expression, and renin activity in the renal cortex and medulla in the clipped kidneys (CK) and nonclipped kidneys (NCK) of 2K1C rats. After 3 wk of unilateral renal clipping, systolic blood pressure and plasma renin activity increased in 2K1C rats (n = 11) compared with sham rats (n = 9). Renal medullary angiotensin peptide levels were increased in 2K1C rats [ ANG I: (CK = 171 +/- 4; NCK = 251 +/- 8 vs. sham = 55 +/- 3 pg/g protein; P < 0.05); ANG II: (CK = 558 +/- 79; NCK = 328 +/- 18 vs. sham = 94 +/- 7 pg/g protein; P < 0.001)]; and ANG 1-7 levels decreased (CK = 18 +/- 2; NCK = 19 +/- 2 pg/g vs. sham = 63 +/- 10 pg/g; P < 0.001). in renal medullas of both kidneys of 2K1C rats, ACE mRNA levels and activity increased but ACE2 decreased. in further studies, we compared renal ACE and ACE2 mRNA levels and their activities from chronic ANG II-infused (n = 6) and sham-operated rats (n = 5). Although the ACE mRNA levels did not differ between ANG II rats and sham rats, the ANG II rats exhibited greater ACE activity and reduced ACE2 mRNA levels and activity. Renal medullary renin activity was similar in the CK and NCK of 2K1C rats but higher compared with sham. Thus, the differential regulation of ACE and ACE2 along with the upregulation of CD renin in both the CK and NCK in 2K1C hypertensive rats indicates that they are independent of perfusion pressure and contribute to the altered content of intrarenal ANG II and ANG 1-7.Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USATulane Univ, Hlth Sci Ctr, Hypertens & Renal Ctr, New Orleans, LA 70112 USAUniv Fed Rio de Janeiro, Biomed Sci Inst, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Nephrol Div, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Nephrol Div, Dept Med, São Paulo, BrazilWeb of ScienceNational Heart, Lung, and Blood InstituteNational Center for Research ResourcesEunice Kennedy Shriver National Institute of Child Health & Human DevelopmentAmerican Heart AssociationCoordinacion de Apoyo de Personas de Educacion Superior PostDoctoral Fellowship from BrazilNational Heart, Lung, and Blood Institute: HL-26731National Center for Research Resources: P20-RR-017659Eunice Kennedy Shriver National Institute of Child Health & Human Development: K12HD043451American Heart Association: 09BGIA228044
Effect of β-Blockers, Angiotensin II, AT2R agonists, and AT1R- and AT2R-antagonists on cell viability in HL-1 cardiomyocytes.
No full text<p>Changes in cell viability of serum starved HL-1 cardiomyocytes in response to treatment by U73122 and β-Blockers (A), and Ang II, Ang II+ losartan, Ang II+ PD123319, and AT2R agonists (B) as determined by the MTS proliferation assay. <b>(A)</b> As expected, phospholipase C inhibition by U73122 showed a strong suppression of cell viability. Treatment with β-Blockers did not result in any significant difference in cell viability compared to DMSO treated control. <b>(B)</b> Treatment NP-6A4 showed the greatest increase in cell viability. Data for A and B are presented as means ± SEM, n≥3 for all treatments, *p<0.05 compared to control as determined by One-way ANOVA followed by the LSD post-hoc test.</p
<i>CXCL8</i> translation and expression is elevated in HL-60 macrophages.
No full text(A and B)CXCL8 and IL6 expression levels in HL-60 macrophages (HL-60 Mac), neutrophil-like HL-60 polymorphonuclear leukocytes (HL-60 PMNs), A549 and H1299 lung epithelial carcinoma cells (A549 ECs), and KHYG-1 NK cells. Expression was measured at resting state (not treated, NT) or after overnight activation with 100 ng/mL LPS or 10 ng/mL TNF. Protein levels were determined via ELISA. The mRNA levels were determined via real-time PCR and presented as the ratio of IL6 or CXCL8 divided by the internal control genes, RPL27. (C) Polysome profiles of HL-60 Mac, A549 EC and KHYG-1 NK cells were obtained from a continuous sucrose density gradient (left to right: 10–50% sucrose). Compared to A549 EC and KHYG-1 NK cells, a lower proportion of the global mRNA (detected at A260) of HL-60 Mac was detected (at A260) in the high sucrose density fractions associated with polysomes. This is indicative of a low translation rate which may be due to the tendency of HL-60 cells to clump upon differentiation into macrophage (S1B Fig). From 14 fractions spanning the entire sucrose gradient, the levels of specific mRNAs (CXCL8, RPL27 and ACTB) were quantified via real-time PCR and presented as a percentage of the sum of all fractions. (A to C) Each graph symbol (squares, inverted-triangles or circles) is the result of a replicate experiment. Replicate experiments were performed on different days. ND: Not detected.</p
- …
