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.
Keywords: Cholelithiasis, cholesterol synthesis, cholesterol absorption, enterohepatic circulation, metabolic syndrome, Niemann- Pick C1-like 1, obesity.
Current Medicinal Chemistry
Title:Therapeutic Reflections in Cholesterol Homeostasis and Gallstone Disease: A Review
Volume: 21 Issue: 12
Author(s): Agostino Di Ciaula, David Q.-H. Wang, Gabriella Garruti, Helen H. Wang, Ignazio Grattagliano, Ornella de Bari and Piero Portincasa
Affiliation:
Keywords: Cholelithiasis, cholesterol synthesis, cholesterol absorption, enterohepatic circulation, metabolic syndrome, Niemann- Pick C1-like 1, obesity.
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.
Export Options
About this article
Cite this article as:
Ciaula Di Agostino, Wang Q.-H. David, Garruti Gabriella, Wang H. Helen, Grattagliano Ignazio, Bari de Ornella and Portincasa Piero, Therapeutic Reflections in Cholesterol Homeostasis and Gallstone Disease: A Review, Current Medicinal Chemistry 2014; 21 (12) . https://dx.doi.org/10.2174/09298673113206660271
DOI https://dx.doi.org/10.2174/09298673113206660271 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Possible Exploitation of Non-Neuronal and Non-Chemical Synaptic Signalling Pathways in Epilepsy Therapy
Current Signal Transduction Therapy Role of FK506 Binding Proteins in Neurodegenerative Disorders
Current Medicinal Chemistry Crosstalk between Inflammation and Coagulation: The Lessons of Sepsis
Current Vascular Pharmacology Pharmacokinetic Profiles of Anticancer Herbal Medicines in Humans and the Clinical Implications
Current Medicinal Chemistry Intervention of Toll-like Receptor-Mediated Human Innate Immunity and Inflammation by Synthetic Compounds and Naturally Occurring Products
Current Medicinal Chemistry Insulin Resistance, Oxidative Stress and Cardiovascular Complications: Role of Sirtuins
Current Pharmaceutical Design New Developments in Antimicrobial Use in Sepsis
Current Pharmaceutical Design IgA Nephropathy: Clinical Significance of Urinary Proteins/Polypeptides Characterization
Current Proteomics An Overall Picture of Chemokine Receptors: Basic Research and Drug Development
Current Pharmaceutical Design Targeting Purine and Pyrimidine Metabolism in Human Apicomplexan Parasites
Current Drug Targets Soy Isoflavones and Exercise: Possible Benefits for Postmenopausal Womens Cardiovascular Health
Current Women`s Health Reviews A Study of Tryptophan Metabolism via Serotonin in Ventricular Cerebrospinal Fluid in HIV-1 Infection Using a Neuroendoscopic Technique
Current HIV Research Genetics and Genomics of Hepatic Acute Phase Reactants: A Mini-Review
Inflammation & Allergy - Drug Targets (Discontinued) Dynamic Factors Controlling Targeting Nanocarriers to Vascular Endothelium
Current Drug Metabolism There is a Link Between Erectile Dysfunction and Heart Failure: It could be Inflammation
Current Drug Targets Investigating Drug-induced Mitochondrial Toxicity: A Biosensor to Increase Drug Safety?
Current Drug Safety Jembrana Disease Virus: Host Responses, Viral Dynamics and Disease Control
Current HIV Research The Genetic Basis of Human Cytomegalovirus Resistance and Current Trends in Antiviral Resistance Analysis
Infectious Disorders - Drug Targets The Ubiquitin-Proteasome System and Proteasome Inhibitors in Central Nervous System Diseases
Cardiovascular & Hematological Disorders-Drug Targets Molecular Biology of Nucleoside Transporters and their Distributions and Functions in the Brain
Current Topics in Medicinal Chemistry