Smooth muscle function and dysfunction in gallbladder disease

Portincasa, Piero; Ciaula, Agostino Di; vanBerge-Henegouwen, Gerard P.

doi:10.1007/s11894-004-0043-0

Cited by 59 publications

(40 citation statements)

References 122 publications

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“…1,2,30 It has become increasingly evident that the gallbladder epithelium could actively modify the lipid compositions of bile by secretion and absorption of lipids and water. 31,32 Cholesterol-supersaturated bile facilitates gallbladder absorption of cholesterol and enhances the accumulation of excess cholesterol in the gallbladder wall. 1,2 Because gallbladder absorptive cells apparently cannot assemble lipoproteins for lipid transport into plasma, the absorbed cholesterol is converted to cholesteryl ester and stored in the mucosa and lamina propria.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ezetimibe on the Prevention and Dissolution of Cholesterol Gallstones

et al. 2008

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Background & Aims-Cholesterol cholelithiasis is one of the most prevalent and most costly digestive diseases in developed countries and its incidence has markedly increased in Asian countries due to the adoption of Western-type dietary habits. Because animal experiments showed that high efficiency of intestinal cholesterol absorption contributes to gallstone formation, we explored whether the potent cholesterol absorption inhibitor ezetimibe could prevent gallstones and promote gallstone dissolution in mice and reduce biliary cholesterol content in humans.

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Section: Discussionmentioning

confidence: 99%

Effect of Ezetimibe on the Prevention and Dissolution of Cholesterol Gallstones

et al. 2008

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“…Defective gallbladder motility has also been suggested as a pathway [43][44][45]. Hyperinsulinemia associated with insulin resistance has been shown to increase oxidative stress in tissues [46], which, in turn, causes damage to transmembrane receptors, including cholecystokinin receptor, and thereby causes dysfunctional contractility of gallbladder [47]. It is noteworthy that increased free fatty acid influx and insulin resistance is associated with abdominal obesity.…”

Section: Obesity and Gallbladder Diseasementioning

confidence: 99%

Steatocholecystitis and Fatty Gallbladder Disease

Tsai

2008

Dig Dis Sci

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Obesity has become an epidemic worldwide. It is accompanied by a multitude of medical complications including metabolic syndrome. Obesity may lead to fatty infiltration of multiple internal organs including liver, heart, kidney, and pancreas, causing organ dysfunctions. Fatty infiltration leads to chronic inflammation and tissue damage. Fatty infiltration in the liver results in nonalcoholic fatty liver disease, which is increasingly common nowadays. Recent studies in animals and humans indicate that obesity also is associated with fatty infiltration of gallbladder, resulting in cholecystosteatosis. The increased gallbladder lipids include free fatty acids, phospholipids, and triglycerides. Enhanced inflammation with an increased amount of fat in the gallbladder results in an abnormal wall structure and decreased contractility. In support of this notion, a recent experiment on the effect of Ezetimibe, which is a novel drug that inhibits intestinal fat absorption, on fatty gallbladder disease reveals that Ezetimibe can ameliorate cholecystosteatosis and restore in vivo gallbladder contractility. The proportion of cholecystectomies performed for chronic acalculous cholecystitis has increased significantly over the past two decades. An increase in gallbladder fat, which leads to poor gallbladder emptying and biliary symptoms, may partly explain this phenomenon. Although dietary carbohydrates have been demonstrated to be associated with fatty gallbladder disease, other potential modifiable environmental factors are not clear. The pathogenesis and prognosis of fatty gallbladder disease, including steatocholecystitis, and the relations of fatty gallbladder disease to nonalcoholic fatty liver disease, including steatohepatitis, and other components of metabolic syndrome are largely unknown. More research is needed to answer these questions.

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“…Malformation of the gallbladder and bile ducts can cause disease, including cholesterol gallstones, chronic inflammation and biliary atresia (reviewed by Portincasa et al, 2004Portincasa et al, , 2008Asai et al, 2015). Congenital biliary atresia is a rare condition in newborn infants (Kohsaka et al, 2002;MieliVergani and Vergani, 2009) that causes inflammation in the bile ducts and liver due to the blockage of bile flow (cholestasis).…”

Section: Introductionmentioning

confidence: 99%

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

et al. 2017

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The gallbladder excretes cytotoxic bile acids into the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos, but the molecular and cellular mechanisms underlying this remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in Sox17 +/− embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders. The embryonic hepatitis showed positive correlations with the severity of cholecystitis in individual Sox17+/− embryos. Embryonic hepatitis could be induced by conditional deletion of Sox17 in the primordial gallbladder epithelia but not in fetal liver hepatoblasts. The Sox17 +/− gallbladder also showed a drastic reduction in sonic hedgehog expression, leading to aberrant smooth muscle formation and defective contraction of the fetal gallbladder. The defective gallbladder contraction positively correlated with the severity of embryonic hepatitis in Sox17 +/− embryos, suggesting a potential contribution of embryonic cholecystitis and fetal gallbladder contraction in the early pathogenesis of congenital biliary atresia.

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Smooth muscle function and dysfunction in gallbladder disease

Cited by 59 publications

References 122 publications

Effect of Ezetimibe on the Prevention and Dissolution of Cholesterol Gallstones

Effect of Ezetimibe on the Prevention and Dissolution of Cholesterol Gallstones

Steatocholecystitis and Fatty Gallbladder Disease

Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia

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