Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol

The New England Journal of Medicine
E ReihnérB Angelin

Abstract

Inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, are now used frequently to treat hypercholesterolemia. We studied the effects of specific inhibition of cholesterol synthesis by one of these agents (pravastatin) on the hepatic metabolism of cholesterol in patients with gallstone disease who were scheduled to undergo cholecystectomy. Ten patients were treated with pravastatin (20 mg twice a day) for three weeks before cholecystectomy; 20 patients not treated served as controls. A liver specimen was obtained from each patient at operation, and the activities of rate-determining enzymes in cholesterol metabolism as well as low-density-lipoprotein (LDL)-receptor binding activity were determined. Pravastatin therapy reduced plasma total cholesterol by 26 percent and LDL cholesterol by 39 percent (P less than 0.005). Serum levels of free lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, decreased by 63 percent (P less than 0.005), indicating reduced de novo biosynthesis of cholesterol. Microsomal HMG-CoA reductase activity, when analyzed in vitro in the absence of the inhibitor, was increased 11...Continue Reading

References

Jun 1, 1979·European Journal of Clinical Investigation·B AngelinB Leijd
Nov 3, 1975·Clinica Chimica Acta; International Journal of Clinical Chemistry·A RodaL Barbara
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M J RudlingB Angelin
Apr 1, 1989·Scandinavian Journal of Clinical and Laboratory Investigation·E LundI Bjorkhem
Sep 1, 1988·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·W C DuaneR L Gebhard
Jul 7, 1988·The New England Journal of Medicine·S M Grundy
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P T MaM S Brown
Mar 6, 1985·Biochimica Et Biophysica Acta·M J Rudling, C O Peterson
Jan 1, 1973·Journal of Clinical Pathology. Supplement (Association of Clinical Pathologists)·K Carlson
Jul 31, 1974·Clinica Chimica Acta; International Journal of Clinical Chemistry·I BjörkhemL Svensson
Feb 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·P T KovanenM S Brown
Apr 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S M Grundy, D W Bilheimer
Jul 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·D W BilheimerJ L Goldstein
Aug 1, 1981·Archives of Internal Medicine·T GordonT R Dawber

❮ Previous
Next ❯

Citations

Mar 21, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T E MiettinenT A Miettinen
Jul 1, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G KallienJ Scheibner
Jan 1, 1992·European Journal of Clinical Pharmacology·H Vanhanen, T A Miettinen
Jan 1, 1995·Journal of Cancer Research and Clinical Oncology·A Gebhardt, A Niendorf
Dec 21, 2006·Pharmaceutical Research·Kari T Kivistö, Mikko Niemi
Aug 13, 2003·Current Atherosclerosis Reports·Ulrich Laufs, James K Liao
Jan 1, 1995·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·A CorsiniA L Catapano
Apr 4, 1997·European Journal of Pharmacology·T Fujioka, Y Tsujita
May 9, 2002·Atherosclerosis·Isabelle LemieuxJean Pierre Després
Dec 1, 1990·Baillière's Clinical Endocrinology and Metabolism·M J Tikkanen
Apr 27, 2013·Journal of Agricultural and Food Chemistry·Lei ZhangXiong Liu
Jun 26, 1998·British Journal of Pharmacology·M HarschA Niendorf
Dec 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Anders BerkenstamJohn D Baxter
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M RudlingB Angelin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.