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simvastatin portal hypertension

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https://www.readbyqxmd.com/read/26321186/three-months-of-simvastatin-therapy-vs-placebo-for-severe-portal-hypertension-in-cirrhosis-a-randomized-controlled-trial
#1
RANDOMIZED CONTROLLED TRIAL
Priscila Pollo-Flores, Mônica Soldan, Ubiratan Cassano Santos, Danielle Gobbi Kunz, Denise Espindola Mattos, Alexandre Cerqueira da Silva, Roberta Cabral Marchiori, Guilherme Ferreira da Motta Rezende
BACKGROUND: Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension. AIM: We evaluated the effects of simvastatin on hepatic venous pressure gradient (HVPG) and azygos vein blood flow in cirrhotic patients. METHODS: A 3-month prospective, randomized, triple-blind trial with simvastatin (40 mg/day) vs. placebo was conducted in patients with cirrhotic portal hypertension. HVPG and azygos blood flow, measured by colour Doppler endoscopic ultrasound, were assessed before and after treatment...
November 2015: Digestive and Liver Disease
https://www.readbyqxmd.com/read/26159269/therapies-drugs-scopes-and-transjugular-intrahepatic-portosystemic-shunt-when-and-how
#2
Juan G Abraldes, Puneeta Tandon
Variceal bleeding is the most serious complication of portal hypertension. All cirrhotic patients should be screened endoscopically for varices which are present in about 30% of compensated and 60% of decompensated patients at diagnosis. In patients without varices, endoscopy surveillance should be continued every 2 years. Patients with high-risk varices (moderate or large in size, or with red color signs, or in Child-Pugh C patients) should be treated with a nonselective β-blocker to prevent bleeding (propranolol, nadolol or carvedilol)...
2015: Digestive Diseases
https://www.readbyqxmd.com/read/26159267/pathophysiology-and-a-rational-basis-of-therapy
#3
Jordi Gracia-Sancho, Raquel Maeso-Díaz, Jaime Bosch
Portal hypertension is a common complication of chronic liver disease. Its relevance comes from the fact that it determines most complications leading to death or liver transplantation in patients with cirrhosis of the liver: bleeding from esophageal or gastric varices, ascites and renal dysfunction, sepsis and hepatic encephalopathy. Portal hypertension results from increased resistance to portal blood flow through the cirrhotic liver. This is caused by two mechanisms: (1) distortion of the liver vascular architecture due to the liver disease causing structural abnormalities (nodule formation, remodeling of liver sinusoids, fibrosis, angiogenesis and vascular occlusion), and (2) increased hepatic vascular tone due to sinusoidal endothelial dysfunction, which results in a defective production of endogenous vasodilators, mainly nitric oxide (NO), and increased production of vasoconstrictors (thromboxane A2, cysteinyl leukotrienes, angiotensin II, endothelins and an activated adrenergic system)...
2015: Digestive Diseases
https://www.readbyqxmd.com/read/25659387/simvastatin-suppresses-the-proangiogenic-microenvironment-of-human-hepatic-stellate-cells-via-the-kruppel-like-factor-2-pathway
#4
Qing Miao, Xiaoqing Zeng, Guifen Ma, Na Li, Yimei Liu, Tiancheng Luo, Jingjing Lian, Shiyao Chen
BACKGROUND AND AIMS: Statins are reported to have a beneficial effect on portal hypertension (PTH); however, the exact mechanism remains unknown. Hepatic stellate cells (HSCs) can be activated by transforming growth factor beta (TGFâ) and play an important role in angiogenesis leading to PTH. Statins potently stimulate the transcription factor, Kruppel-like factor 2 (KLF2), which can negatively regulate angiogenesis. Our present study aimed to investigate the anti-angiogenic potential of statins in HSCs through the KLF2 pathway...
February 2015: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/25659386/simvastatin-from-cholesterol-to-nitric-oxide-from-ischemic-heart-disease-to-portal-hypertension
#5
EDITORIAL
J A Solís-Herruzo, P Solís-Muñoz
No abstract text is available yet for this article.
February 2015: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/25500203/klf2-exerts-antifibrotic-and-vasoprotective-effects-in-cirrhotic-rat-livers-behind-the-molecular-mechanisms-of-statins
#6
COMPARATIVE STUDY
Giusi Marrone, Raquel Maeso-Díaz, Guillermo García-Cardena, Juan G Abraldes, Juan Carlos García-Pagán, Jaime Bosch, Jordi Gracia-Sancho
OBJECTIVE: In the liver, the transcription factor, Kruppel-like factor 2 (KLF2), is induced early during progression of cirrhosis to lessen the development of vascular dysfunction; nevertheless, its endogenous expression results insufficient to attenuate establishment of portal hypertension and aggravation of cirrhosis. Herein, we aimed to explore the effects and the underlying mechanisms of hepatic KLF2 overexpression in in vitro and in vivo models of liver cirrhosis. DESIGN: Activation phenotype was evaluated in human and rat cirrhotic hepatic stellate cells (HSC) treated with the pharmacological inductor of KLF2 simvastatin, with adenovirus codifying for this transcription factor (Ad-KLF2), or vehicle, in presence/absence of inhibitors of KLF2...
September 2015: Gut
https://www.readbyqxmd.com/read/23672611/effects-of-simvastatin-on-the-portal-systemic-collateral-vascular-response-to-endothelin-1-and-shunting-degree-in-portal-hypertensive-rats
#7
Shao-Jung Hsu, Sang-Sun Wang, I-Fang Hsin, Hui-Chun Huang, Fa-Yauh Lee, Jing-Yi Lee, Han-Chieh Lin, Chiao-Lin Chuang, Shou-Dong Lee
OBJECTIVE: Endothelin-1 (ET-1) exerts vasoconstrictive effect on portal-systemic collateral vascular bed of portal hypertensive rats. Statins are lipid-lowering agents with nitric oxide (NO)-related vasodilatory effects. Considering NO-associated vascular hyporesponsiveness to vasoconstrictors and shunting formation in portal hypertension, this study investigated the effects of simvastatin on 1) the portal-systemic collateral vascular responsiveness to ET-1 and 2) the portal-systemic shunting degree...
July 2013: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/22989565/the-transcription-factor-klf2-mediates-hepatic-endothelial-protection-and-paracrine-endothelial-stellate-cell-deactivation-induced-by-statins
#8
Giusi Marrone, Lucia Russo, Eugenio Rosado, Diana Hide, Guillermo García-Cardeña, Juan Carlos García-Pagán, Jaime Bosch, Jorge Gracia-Sancho
BACKGROUND & AIMS: Statins improve hepatic endothelial function and liver fibrosis in experimental models of cirrhosis, thus they have been proposed as therapeutic options to ameliorate portal hypertension syndrome. The transcription factor Kruppel-like factor 2 (KLF2) may be induced by statins in liver sinusoidal endothelial cells (SEC), orchestrating an efficient vasoprotective response. The present study aimed at characterizing whether KLF2 mediates statins-derived hepatic protection...
January 2013: Journal of Hepatology
https://www.readbyqxmd.com/read/21112949/endothelial-expression-of-transcription-factor-kruppel-like-factor-2-and-its-vasoprotective-target-genes-in-the-normal-and-cirrhotic-rat-liver
#9
Jorge Gracia-Sancho, Lucia Russo, Héctor García-Calderó, Joan Carles García-Pagán, Guillermo García-Cardeña, Jaime Bosch
OBJECTIVE: The transcription factor Kruppel-like factor 2 (KLF2) modulates the expression of multiple endothelial vasoprotective genes. In the absence of KLF2, the endothelial phenotype becomes dysfunctional. To date, blood-derived shear stress is the main physiological stimulus identified to trigger and sustain endothelial KLF2 expression. Portal hypertension is a common complication of cirrhosis. Sinusoidal distortion and endothelial dysfunction play a significant role in its pathogenesis...
April 2011: Gut
https://www.readbyqxmd.com/read/20659230/simvastatin-effects-on-portal-systemic-collaterals-of-portal-hypertensive-rats
#10
Hui-Chun Huang, Sun-Sang Wang, Jing-Yi Lee, Yi-Chou Chen, Fa-Yauh Lee, Han-Chieh Lin, Ching-Chih Chang, Shou-Dong Lee
BACKGROUND AND AIM: Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals. METHODS: Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from -2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i...
August 2010: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/19208350/simvastatin-lowers-portal-pressure-in-patients-with-cirrhosis-and-portal-hypertension-a-randomized-controlled-trial
#11
RANDOMIZED CONTROLLED TRIAL
Juan G Abraldes, Agustin Albillos, Rafael Bañares, Juan Turnes, Rosario González, Juan Carlos García-Pagán, Jaime Bosch
BACKGROUND & AIMS: Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension. METHODS: Fifty-nine patients with cirrhosis and portal hypertension (HVPG > or =12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial...
May 2009: Gastroenterology
https://www.readbyqxmd.com/read/17335931/simvastatin-treatment-improves-liver-sinusoidal-endothelial-dysfunction-in-ccl4-cirrhotic-rats
#12
Juan G Abraldes, Aina Rodríguez-Vilarrupla, Mariona Graupera, Carmen Zafra, Héctor García-Calderó, Juan Carlos García-Pagán, Jaime Bosch
BACKGROUND/AIMS: Sinusoidal endothelial dysfunction with decreased nitric oxide (NO) production contributes to increased hepatic resistance in cirrhosis. Statins improve endothelial dysfunction in peripheral vasculature. This study was designed to characterize the hemodynamic and molecular effects of statins in cirrhotic rats. METHODS: Systemic and splanchnic hemodynamics were evaluated in CCl(4) ascitic cirrhotic rats treated with placebo or simvastatin (25 mg/kg/day, for 3 days), at baseline and after volume expansion...
June 2007: Journal of Hepatology
https://www.readbyqxmd.com/read/14988829/simvastatin-enhances-hepatic-nitric-oxide-production-and-decreases-the-hepatic-vascular-tone-in-patients-with-cirrhosis
#13
RANDOMIZED CONTROLLED TRIAL
Carmen Zafra, Juan G Abraldes, Juan Turnes, Annalisa Berzigotti, Mercedes Fernández, Juan C Garca-Pagán, Juan Rodés, Jaime Bosch
BACKGROUND & AIMS: In cirrhosis, an insufficient release of nitric oxide contributes to increased hepatic resistance and portal pressure and enhances the postprandial increase in portal pressure. We hypothesized that simvastatin, which enhances Akt-dependent endothelial nitric oxide synthase phosphorylation, may increase hepatic nitric oxide release and decrease hepatic resistance in patients with cirrhosis and portal hypertension. METHODS: In protocol 1, 13 patients had measurements of the hepatic venous pressure gradient, hepatic blood flow, mean arterial pressure, cardiac output, and nitric oxide products before and 30 and 60 minutes after 40 mg of simvastatin...
March 2004: Gastroenterology
https://www.readbyqxmd.com/read/9210625/effects-of-simvastatin-pentoxifylline-and-spironolactone-on-hepatic-fibrosis-and-portal-hypertension-in-rats-with-bile-duct-ligation
#14
F Oberti, C Pilette, H Rifflet, M Y Maïga, A Moreau, Y Gallois, A Girault, A le Bouil, J J Le Jeune, J L Saumet, G Feldmann, P Calès
AIMS/METHODS: Our aim was to study the antifibrotic and hemodynamic effects of simvastatin (SMV), pentoxifylline (PTX) and spironolactone (SPN), three drugs which may have antifibrotic and/or portal hypotensive properties, in a model of hepatic fibrosis and portal hypertension induced in rats by bile duct ligation. A blind study was performed in five groups of 53 Sprague-Dawley rats: sham, placebo (PL), SMV (2.5 mg x kg(-1) x J(-1)), PTX (50 mg x kg(-1) x J(-1)) and SPN (100 mg x kg(-1) x J(-1))...
June 1997: Journal of Hepatology
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