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Condition: Hypertension

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Total 587 results found since Jan 2013.

Cyclic Stretch Stimulates Mitochondrial Reactive Oxygen Species and Nox4 Signaling in Pulmonary Artery Smooth Muscle Cells.
This study was designed to determine if cyclic stretch induces a persistent pulmonary hypertension of the newborn (PPHN) phenotype of increased NADPH oxidase (Nox) 4 signaling in control pulmonary artery smooth muscle cells (PASMC), and to identify the signal transduction molecules involved. To achieve this, PPHN was induced in lambs by antenatal ligation of the ductus arteriosus at 128 days gestation. After 9 days, lungs and PASMC were isolated from control (twin) and PPHN lambs. Control PASMC were exposed to cyclic stretch at 1Hz and 15% elongation for 24h. Stretch-induced Nox4 expression was attenuated by inhibition of ...
Source: Am J Physiol Lung Ce... - May 29, 2015 Category: Respiratory Medicine Authors: Wedgwood S, Lakshminrusimha S, Schumacker PT, Steinhorn RH Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Shear Stress-Induced Mitochondrial Biogenesis Decreases the Release of Microparticles from Endothelial Cells.
Abstract The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in pre...
Source: American Journal of Physiology. Heart and Circulatory Physiology - May 29, 2015 Category: Physiology Authors: Kim JS, Kim B, Lee H, Thakkar S, Babbitt DM, Eguchi S, Brown MD, Park JY Tags: Am J Physiol Heart Circ Physiol Source Type: research

RNAseq Reveals a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension.
CONCLUSIONS: The novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension. PMID: 26030479 [PubMed - as supplied by publisher]
Source: American Journal of Respiratory and Critical Care Medicine - June 1, 2015 Category: Respiratory Medicine Authors: Rhodes CJ, Im H, Cao A, Hennigs JK, Wang L, Sa S, Chen PI, Nickel NP, Miyagawa K, Hopper RK, Tojais NF, Li CG, Gu M, Spiekerkoetter E, Xian Z, Chen R, Zhao M, Kaschwich M, Del Rosario PA, Bernstein D, Zamanian RT, Wu JC, Snyder M, Rabinovitch M Tags: Am J Respir Crit Care Med Source Type: research

Abstract 5109: The CARMA3-Bcl10-MALT1 signalosome mediates NF-{kappa}B activation and cellular invasion in AGTR1-positive breast cancer
Angiotensin II (Ang II) is a potent vasoconstrictor and vascular pro-inflammatory mediator, known classically for its role in promoting arterial dysfunction. Many of these pathogenic effects result from activation of NF-κB in response to stimulation of the type-1 Ang II receptor (AGTR1), a G protein-coupled receptor. We previously discovered that a complex composed of three proteins, CARMA3, Bcl10 and MALT1 (CBM signalosome) mediates AGTR1-dependent activation of NF-κB in vascular cells. Despite its principal role in vascular pathobiology, we recently found that AGTR1 is aberrantly overexpressed in 10-20% of breast cance...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ekambaram, P., Hubel, N., Lee, J.-Y., Klei, L., Concel, V., Delekta, P., Tomlins, S., McAllister-Lucas, L., Lucas, P. Tags: Tumor Biology Source Type: research

A functional tandem between transient receptor potential canonical channels 6 and calcium-dependent chloride channels in Human epithelial cells.
In conclusion, we show that TRPC6 channel is pivotal for the activation of CaCC by guanabenz through a α2-adrenergic-independent pathway in human airway epithelial cells. We suggest propose a functional coupling between TRPC6 and CaCC and guanabenz as a potential TRPC6 activator for exploring TRPC6 and CaCC channel functions and corresponding channelopathies. PMID: 26265544 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - August 8, 2015 Category: Drugs & Pharmacology Authors: Bertrand J, Dannhoffer L, Antigny F, Vachel L, Jayle C, Vandebrouck C, Becq F, Norez C Tags: Eur J Pharmacol Source Type: research

Increased S100A4 expression in the vasculature of human COPD lungs and murine model of smoke-induced emphysema
Conclusions: As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients.
Source: Respiratory Research - October 20, 2015 Category: Respiratory Medicine Authors: Sebastian ReimannLudger FinkJochen WilhelmJulia HoffmannMariola BednorzMichael SeimetzIsabel DessureaultRoger TroesserBahil GhanimWalter KlepetkoWerner SeegerNorbert WeissmannGrazyna Kwapiszewska Source Type: research

Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway Original Articles
Conclusions— Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases.
Source: Circulation: Cardiovascular Genetics - October 20, 2015 Category: Cardiology Authors: Fedorova, O. V., Zernetkina, V. I., Shilova, V. Y., Grigorova, Y. N., Juhasz, O., Wei, W., Marshall, C. A., Lakatta, E. G., Bagrov, A. Y. Tags: Etiology, Hypertension Original Articles Source Type: research

Abstract 100: Sorting Nexin 1: Molecular Mechanisms and Pharmacogenomics Session Title: Concurrent XVI A: Oxidative Stress I
Sorting nexin 1 (SNX1) plays a pivotal role for the normal activity of renal dopamine D5 receptor (D5R). Kidney-restricted, Snx1-siRNA depletion of SNX1 results in impaired natriuretic response to salt load and hypertension in mice. Genetic ablation of the Snx1 gene (Snx1-/-) resulted in increased oxidative stress, impaired sodium excretion, and elevated systolic blood pressure (SBP, 131.3±6.4 mm Hg, n=5) in mice. The D5R has antioxidant properties by negatively regulating the expression of the NADPH oxidase (NOX). We found that NOX1, NOX2, and p47phox, as well as the antioxidant PON2, conceivably as compensation, w...
Source: Hypertension - November 3, 2015 Category: Cardiology Authors: Yang, J., Asico, L., Beitelshees, A., Wang, X., Jones, J., Armando, I., Cuevas, S., Zeng, C., Felder, R., Weinman, E., Jose, P., Villar, V. A. M. Tags: Session Title: Concurrent XVI A: Oxidative Stress I Source Type: research

Abstract P180: Dopamine D2 Receptors Regulate Wnt Signaling and Apoptosis in Human Renal Proximal Tubule Cells Session Title: Genetics, Epigenetics, Proteomics and Metabolomics
Previous work from our laboratory indicates that the dopamine D2 receptor (D2R) in the kidney has a direct role in regulating renal inflammation and injury and blood pressure. Some common single nucleotide polymorphisms (D2R SNPs; rs 6276, 6277, and 1800497) in the human DRD2 gene are associated with decreased D2R expression and function. Immortalized renal proximal tubule cells (RPTCs) from subjects carrying D2R SNPs (RPTC-D2R SNPs) express less D2Rs than RPTCs carrying no D2R SNPs (RPTC-D2R WT) (62±4 vs 100±6%; P<0.04) and a pro-inflammatory and pro-fibrotic phenotype with markers of epithelial mesenchym...
Source: Hypertension - November 3, 2015 Category: Cardiology Authors: Han, F., Zhang, Y., Konkalmatt, P., Jones, J. E., Gildea, J., Felder, R. A., Jose, P. A., Armando, I. Tags: Session Title: Genetics, Epigenetics, Proteomics and Metabolomics Source Type: research

PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling.
Abstract Endothelial dysfunction, characterized by impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued decrease of NO production, is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Laminar blood flow-mediated specific signaling cascades modulate vascular endothelial cells (ECs) structure and functions. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation in ECs, which in part confers laminar flow atheroprotective action. However, the molecular mechanisms where...
Source: Cellular Signalling - December 16, 2015 Category: Cytology Authors: Xu S, Ha CH, Wang W, Xu X, Yin M, Jin FQ, Mastrangelo M, Koroleva M, Fujiwara K, Jin ZG Tags: Cell Signal Source Type: research

Pathogenic Role of Calcium-sensing Receptors in the Development and Progression of Pulmonary Hypertension.
Abstract An increase in [Ca(2+)]cyt in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and a critical stimulation for PASMC proliferation and migration. We previously demonstrated that expression and function of calcium sensing receptors (CaSR) in PASMC from patients with IPAH and animals with experimental PH were greater than in PASMC from normal subjects and control animals. However, the mechanisms by which CaSR triggers Ca(2+) influx in PASMC and the implication of CaSR in the development of PH remain elusive. Here we report that CaSR functionally interacts with ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 11, 2016 Category: Cytology Authors: Tang H, Yamamura A, Yamamura H, Song S, Fraidenburg DR, Chen J, Gu Y, Pohl NM, Zhou T, Jiménez-Pérez L, Ayon RJ, Desai AA, Goltzman D, Rischard F, Khalpey ZI, Black SM, Garcia JG, Makino A, Yuan JX Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

Id: 119: pathogenic roles of calcium-sensing receptors and transient receptor potential canonical channels 6 in the development and progression of pulmonary hypertension
Conclusions These data indicate that functional interaction of upregulated CaSR and upregulated TRPC6 in PASMC from IPAH patients and animals with experimental PH may play an important role in the development and progression of sustained pulmonary vasoconstriction and pulmonary vascular remodeling. Blockade or downregulation of CaSR and/or TRPC6 with siRNA or miRNA may be a novel therapeutic strategy to develop new drugs for patients with pulmonary arterial hypertension. Keywords G protein-coupled receptor; ionic ligand; hypoxia-induced pulmonary hypertension.
Source: Journal of Investigative Medicine - March 21, 2016 Category: Research Authors: TANG, H., Gu, Y., Black, S., Garcia, J., Makino, A., Yuan, J., Yamamura, A., Fraidenburg, D., Chen, J. Tags: Pulmonary/Critical Care Source Type: research

Carfilzomib reverses pulmonary arterial hypertension
Conclusion The addition of anti-tumour agents such as CFZ along with cardioprotectants to currently available vasodilators may be a promising way to improve PAH therapy.
Source: Cardiovascular Research - April 18, 2016 Category: Cardiology Authors: Wang, X., Ibrahim, Y. F., Das, D., Zungu-Edmondson, M., Shults, N. V., Suzuki, Y. J. Tags: Integrative physiology and pathophysiology Source Type: research

Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension
An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and a critical stimulation for PASMC proliferation and migration. Previously, we demonstrated that expression and function of calcium sensing receptors (CaSR) in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH) and animals with experimental pulmonary hypertension (PH) were greater than in PASMC from normal subjects and control animals. However, the mechanisms by which CaSR triggers Ca2+ influx in PASMC and the implication of CaSR in the de...
Source: AJP: Lung Cellular and Molecular Physiology - April 30, 2016 Category: Respiratory Medicine Authors: Tang, H., Yamamura, A., Yamamura, H., Song, S., Fraidenburg, D. R., Chen, J., Gu, Y., Pohl, N. M., Zhou, T., Jimenez-Perez, L., Ayon, R. J., Desai, A. A., Goltzman, D., Rischard, F., Khalpey, Z., Black, S. M., Garcia, J. G. N., Makino, A., Yuan, J. X. J. Tags: ARTICLES Source Type: research

Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Co-Repressor C-terminal Binding Protein-1.
CONCLUSIONS: -CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target. PMID: 27562971 [PubMed - as supplied by publisher]
Source: Circulation - August 24, 2016 Category: Cardiology Authors: Li M, Riddle S, Zhang H, D'Alessandro A, Flockton A, Serkova NJ, Hansen KC, Moldvan R, McKeon BA, Frid M, Kumar S, Li H, Liu H, Cánovas A, Medrano JF, Thomas MG, Iloska D, Plecita-Hlavata L, Jezek P, Pullamsetti S, Fini MA, El Kasmi KC, Zhang Q, Stenmark Tags: Circulation Source Type: research