Cholesterol crystal nucleation: A decade-long search for the missing link in gallstone pathogenesis
✍ Scribed by Nezam H. Afdhal; Bernard F. Smith
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 554 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Cholesterol gallstones form after a series of pathological events occurs in both the liver and the gallbladder. These events include hepatic secretion of cholesterol supersaturated bile, nucleation and growth of cholesterol monohydrate crystals in the gallbladder and impaired emptying of gallbladder contents (1). In 1979, nucleation of cholesterol monohydrate crystals was identified as the earliest event in the evolution of cholesterol gallstones that reliably distinguishes patients who form gallstones from normal patients (2). Despite an intensive, decade-long search to identify the factors that influence cholesterol crystal nucleation in lithogenic bile, our understanding of the pathophysiology of cholesterol gallstone formation remains fragmentary and incomplete.
Recent research in cholesterol gallstone pathogenesis has focused on the physical chemistry of cholesterol transport in bile and the role of protein-lipid interactions in promoting cholesterol crystal nucleation. Cholesterol is secreted from the hepatocyte canalicular membrane in unilamellar phospholipid vesicles (31, but the cellular processes responsible for biliary lipid secretion remain unknown. In unsaturated hepatic bile, cholesterolphospholipid vesicles are solubilized by bile salts into mixed lipid micelles that are thermodynamically stable carriers of cholesterol in bile (4). In supersaturated bile, however, cholesterol is also transported in unilamellar phospholipid vesicles that can aggregate and fuse to form large multilamellar vesicles (5-7). Cholesterol monohydrate crystals nucleate from a liquid crystalline phase in these multilamellar vesicles (7,8). Unilamellar vesicle aggregation and fusion appear to be the critical steps in initiating the sequence of physical chemical events leading to cholesterol crystal nucleation (9, 10). Model systems of vesicle fusion using phosphatidylserine vesicles have been developed to study the regulation of biological membrane fusion (1 1-13), but their relevance to the investigation of vesicle fusion in bile is uncertain. The major phospholipid in bile, phosphatidylcholine, behaves in a fundamentally different manner from phosphatidylserine because of the absence Dr.