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10.1164/rccm.201311-2037OC http://scihub22266oqcxt.onion/10.1164/rccm.201311-2037OC 24738736!ä!24738736 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Respir+Crit+Care+Med 2014 ; 189 (11): 1359-73 Nephropedia Template TP {{tp|p=24738736|t=2014. Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema |pdf=|usr=}}{{24738736}} gab.com Text Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema JO: Am J Respir Crit Care Med http://www.kidney.de/pget.php?&tw=1&pmid=24738736 #FOAvip RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress of the disease is available. OBJECTIVES: To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in development of lung emphysema and pulmonary hypertension (PH) and to test whether the sGC-cGMP axis is a treatment target for these conditions. METHODS: Investigations were performed in human lung tissue from patients with COPD, healthy donors, mice, and guinea pigs. Mice were exposed to cigarette smoke (CS) for 6 hours per day, 5 days per week for up to 6 months and treated with BAY 63-2521. Guinea pigs were exposed to CS from six cigarettes per day for 3 months, 5 days per week and treated with BAY 41-2272. Both BAY compounds are sGC stimulators. Gene and protein expression analysis were performed by quantitative real-time polymerase chain reaction and Western blotting. Lung compliance, hemodynamics, right ventricular heart mass alterations, and alveolar and vascular morphometry were performed, as well as inflammatory cell infiltrate assessment. In vitro assays of cell adhesion, proliferation, and apoptosis have been done. MEASUREMENTS AND MAIN RESULTS: The functionally essential sGC beta1-subunit was down-regulated in patients with COPD and in CS-exposed mice. sGC stimulators prevented the development of PH and emphysema in the two different CS-exposed animal models. sGC stimulation prevented peroxynitrite-induced apoptosis of alveolar and endothelial cells, reduced CS-induced inflammatory cell infiltrate in lung parenchyma, and inhibited adhesion of CS-stimulated neutrophils. CONCLUSIONS: The sGC-cGMP axis is perturbed by chronic exposure to CS. Treatment of COPD animal models with sGC stimulators can prevent CS-induced PH and emphysema. Twit Text FOAVip Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema ????Am J Respir Crit Care Med http://www.kidney.de/pget.php?&tw=1&pmid=24738736 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24738736 #FOAvip English Wikipedia <ref>{{Cite pmid|24738736}}</ref> Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema #MMPMID24738736 Weissmann N; Lobo B; Pichl A; Parajuli N; Seimetz M; Puig-Pey R; Ferrer E; Peinado VI; Dominguez-Fandos D; Fysikopoulos A; Stasch JP; Ghofrani HA; Coll-Bonfill N; Frey R; Schermuly RT; Garcia-Lucio J; Blanco I; Bednorz M; Tura-Ceide O; Tadele E; Brandes RP; Grimminger J; Klepetko W; Jaksch P; Rodriguez-Roisin R; Seeger W; Grimminger F; Barbera JA Am J Respir Crit Care Med 2014[Jun]; 189 (11): 1359-73 PMID24738736show ga RATIONALE: Chronic obstructive pulmonary disease (COPD) is a major cause of death worldwide. No therapy stopping progress of the disease is available. OBJECTIVES: To investigate the role of the soluble guanylate cyclase (sGC)-cGMP axis in development of lung emphysema and pulmonary hypertension (PH) and to test whether the sGC-cGMP axis is a treatment target for these conditions. METHODS: Investigations were performed in human lung tissue from patients with COPD, healthy donors, mice, and guinea pigs. Mice were exposed to cigarette smoke (CS) for 6 hours per day, 5 days per week for up to 6 months and treated with BAY 63-2521. Guinea pigs were exposed to CS from six cigarettes per day for 3 months, 5 days per week and treated with BAY 41-2272. Both BAY compounds are sGC stimulators. Gene and protein expression analysis were performed by quantitative real-time polymerase chain reaction and Western blotting. Lung compliance, hemodynamics, right ventricular heart mass alterations, and alveolar and vascular morphometry were performed, as well as inflammatory cell infiltrate assessment. In vitro assays of cell adhesion, proliferation, and apoptosis have been done. MEASUREMENTS AND MAIN RESULTS: The functionally essential sGC beta1-subunit was down-regulated in patients with COPD and in CS-exposed mice. sGC stimulators prevented the development of PH and emphysema in the two different CS-exposed animal models. sGC stimulation prevented peroxynitrite-induced apoptosis of alveolar and endothelial cells, reduced CS-induced inflammatory cell infiltrate in lung parenchyma, and inhibited adhesion of CS-stimulated neutrophils. CONCLUSIONS: The sGC-cGMP axis is perturbed by chronic exposure to CS. Treatment of COPD animal models with sGC stimulators can prevent CS-induced PH and emphysema. |Animals[MESH] |Biomarkers/metabolism[MESH] |Blotting, Western[MESH] |Disease Models, Animal[MESH] |Down-Regulation[MESH] |Emphysema/enzymology/*prevention & control[MESH] |Guanylate Cyclase/*metabolism[MESH] |Guinea Pigs[MESH] |Humans[MESH] |Hypertension, Pulmonary/enzymology/*prevention & control[MESH] |In Vitro Techniques[MESH] |Mice[MESH] |Pulmonary Disease, Chronic Obstructive/enzymology/*prevention & control[MESH] |Real-Time Polymerase Chain Reaction[MESH] |Receptors, Cytoplasmic and Nuclear/*metabolism[MESH] |Smoking/*adverse effects/metabolism[MESH]Stimulation of soluble guanylate cyclase prevents cigarette smoke-indu(epmc).pdf DeepDyve Pubget Overpricing