Abstract
Cholesterol gallstone disease is one of the most prevalent and the most costly digestive diseases in Western countries. Its pathogenesis is a complex paradigm resulting from the interaction of genetic factors, hepatic hypersecretion of cholesterol, increased intestinal absorption of cholesterol, a constantly "supersaturated" bile, crystallization of biliary cholesterol, and gallbladder stasis. De novo cholesterol biosynthesis, biliary cholesterol output, and intestinal cholesterol absorption are therefore key steps involved in cholesterol homeostasis. Establishing the right pharmacological therapy for cholesterol gallstones is of major importance in Western healthcare systems. Certain drugs might independently influence cholesterol gallstone formation by blocking the 3-hydroxy-3-methylglutaryl- coenzyme A reductase and inhibiting cholesterol biosynthesis in the liver (statins) or blocking cholesterol absorption in the small intestine apical membrane by specifically inhibiting the Niemann-Pick C1-like 1 protein (ezetimibe). This review will focus on the possibility that statins and ezetimibe, by acting at different levels of cholesterol homeostasis, might represent novel therapeutic approaches to prevent cholesterol gallstones in selected subjects at risk.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1435-1447 |
| Number of pages | 13 |
| Journal | Current Medicinal Chemistry |
| Volume | 21 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jan 1 2014 |
| Externally published | Yes |
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Keywords
- Cholelithiasis
- Cholesterol absorption
- Cholesterol synthesis
- Enterohepatic circulation
- Metabolic syndrome
- Niemann-Pick C1-like 1
- Obesity
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
Cite this
Therapeutic reflections in cholesterol homeostasis and gallstone disease : A review. / Di Ciaula, Agostino; Wang, David Q.H.; Garruti, Gabriella; Wang, Helen H.; Grattagliano, Ignazio; De Bari, Ornella; Portincasa, Piero.
In: Current Medicinal Chemistry, Vol. 21, No. 12, 01.01.2014, p. 1435-1447.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Therapeutic reflections in cholesterol homeostasis and gallstone disease
T2 - A review
AU - Di Ciaula, Agostino
AU - Wang, David Q.H.
AU - Garruti, Gabriella
AU - Wang, Helen H.
AU - Grattagliano, Ignazio
AU - De Bari, Ornella
AU - Portincasa, Piero
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Cholesterol gallstone disease is one of the most prevalent and the most costly digestive diseases in Western countries. Its pathogenesis is a complex paradigm resulting from the interaction of genetic factors, hepatic hypersecretion of cholesterol, increased intestinal absorption of cholesterol, a constantly "supersaturated" bile, crystallization of biliary cholesterol, and gallbladder stasis. De novo cholesterol biosynthesis, biliary cholesterol output, and intestinal cholesterol absorption are therefore key steps involved in cholesterol homeostasis. Establishing the right pharmacological therapy for cholesterol gallstones is of major importance in Western healthcare systems. Certain drugs might independently influence cholesterol gallstone formation by blocking the 3-hydroxy-3-methylglutaryl- coenzyme A reductase and inhibiting cholesterol biosynthesis in the liver (statins) or blocking cholesterol absorption in the small intestine apical membrane by specifically inhibiting the Niemann-Pick C1-like 1 protein (ezetimibe). This review will focus on the possibility that statins and ezetimibe, by acting at different levels of cholesterol homeostasis, might represent novel therapeutic approaches to prevent cholesterol gallstones in selected subjects at risk.
AB - Cholesterol gallstone disease is one of the most prevalent and the most costly digestive diseases in Western countries. Its pathogenesis is a complex paradigm resulting from the interaction of genetic factors, hepatic hypersecretion of cholesterol, increased intestinal absorption of cholesterol, a constantly "supersaturated" bile, crystallization of biliary cholesterol, and gallbladder stasis. De novo cholesterol biosynthesis, biliary cholesterol output, and intestinal cholesterol absorption are therefore key steps involved in cholesterol homeostasis. Establishing the right pharmacological therapy for cholesterol gallstones is of major importance in Western healthcare systems. Certain drugs might independently influence cholesterol gallstone formation by blocking the 3-hydroxy-3-methylglutaryl- coenzyme A reductase and inhibiting cholesterol biosynthesis in the liver (statins) or blocking cholesterol absorption in the small intestine apical membrane by specifically inhibiting the Niemann-Pick C1-like 1 protein (ezetimibe). This review will focus on the possibility that statins and ezetimibe, by acting at different levels of cholesterol homeostasis, might represent novel therapeutic approaches to prevent cholesterol gallstones in selected subjects at risk.
KW - Cholelithiasis
KW - Cholesterol absorption
KW - Cholesterol synthesis
KW - Enterohepatic circulation
KW - Metabolic syndrome
KW - Niemann-Pick C1-like 1
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=84899823115&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899823115&partnerID=8YFLogxK
U2 - 10.2174/09298673113206660271
DO - 10.2174/09298673113206660271
M3 - Review article
C2 - 24059227
AN - SCOPUS:84899823115
VL - 21
SP - 1435
EP - 1447
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 12
ER -