History And Development Of HMG-CoA Reductase Inhibitors
S. Bellosta, R. Paoletti, A. Corsini
Published 2002 · Medicine
Download PDFAnalyze on Scholarcy
Coronary heart disease (CHD) is the leading cause of mortality in Western countries [1, 2]. A strong, positive correlation between high levels of plasma total and low-density lipoprotein (LDL) cholesterol and CHD is well established . Dietary and/or pharmacological approaches aimed at lowering elevated plasma LDL appears therefore to be a logical intervention to reduce incidence of CHD or even reversing the development of coronary atherosclerosis [1, 4, 5, 6, 7, 8]. A number of cholesterol-lowering drugs are currently available for human use [1, 2, 9]. Among these, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, the so-called statins: atorvastatin, cerivastatinl, fluvastatin, pitavastatin, pravastatin, lovastatin, rosuvastatin and simvastatin, can achieve relatively large reductions in plasma cholesterol levels and are a well-established class of drugs for the treatment of hypercholesterolemia . Clinical trials have demonstrated that they can induce regression of vascular atherosclerosis, as well as reduction of cardiovascular-related morbidity and mortality, in patients with and without coronary artery disease CAD [11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]. These trials provide a powerful endorsement of the value of lipid-lowering therapy with a statin in patients who are at risk for CAD.
This paper references
Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
T. Aoki (1997)
Slow binding inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
P. Louis-Flamberg (1990)
Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.
M. Frick (1987)
Appearance of crystalloid endoplasmic reticulum in compactin-resistant Chinese hamster cells with a 500-fold increase in 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
D. Chin (1982)
Carrier-mediated uptake of pravastatin by rat hepatocytes in primary culture.
T. Komai (1992)
Lipid-lowering and antiatherosclerotic effect of NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in Watanabe heritable hyperlipidemic rabbits.
H. Suzuki (2000)
The intracellular targeting and membrane topology of 3-hydroxy-3-methylglutaryl-CoA reductase.
E. Olender (1992)
Hypolipidemic effect of NK-104 and other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in guinea pigs.
H. Suzuki (2001)
Inhibition of cholesterol synthesis reduces low-density-lipoprotein apoprotein B production without decreasing very-low-density-lipoprotein apoprotein B synthesis in rabbits.
A. L. La Ville (1984)
Atherosclerosis is an inflammatory disease.
R. Ross (1999)
Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase.
M. Brown (1978)
Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: span-wise variations.
M. C. Burleigh (1992)
Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions.
W. Kaesemeyer (1999)
INFLUENCE OF PLAQUE CONFIGURATION AND STRESS DISTRIBUTION ON FISSURING OF CORONARY ATHEROSCLEROTIC PLAQUES
P. Richardson (1989)
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study.
G. Schwartz (2001)
Drug treatment of lipid disorders.
R. Knopp (1999)
Effects of pravastatin on left ventricular mass in patients with hyperlipidemia and essential hypertension.
S. Su (2000)
Prevention of coronary heart disease in clinical practice. Recommendations of the Second Joint Task Force of European and other Societies on coronary prevention.
D. Wood (1998)
Requirement for mevalonate in acetylated LDL induction of cholesterol esterification in macrophages.
F. Bernini (1993)
Lipid Lowering and Plaque Regression New Insights Into Prevention of Plaque Disruption and Clinical Events in Coronary Disease
B. Greg Brown (1993)
A receptor-mediated pathway for cholesterol homeostasis.
M. Brown (1986)
Proapoptotic effect of atorvastatin on stimulated rabbit smooth muscle cells.
R. Baetta (1997)
Lovastatin inhibits gene expression of type-I scavenger receptor in THP-1 human macrophages.
N. Umetani (1996)
Pharmacology of competitive inhibitors of HMG-CoA reductase.
A. Corsini (1995)
Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its mRNA in rat liver as studied with a monoclonal antibody and a cDNA probe.
L. Liscum (1983)
Posttranslational modification of proteins by isoprenoids in mammalian cells
W. Maltese (1990)
Monacolin K, a new hypocholesterolemic agent produced by a Monascus species.
A. Endo (1979)
Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMG-CoA reductase.
A. Corsini (1993)
The structure of the catalytic portion of human HMG-CoA reductase.
E. Istvan (2000)
The discovery and development of HMG-CoA reductase inhibitors.
A. Endo (1992)
HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages.
S. Bellosta (1998)
Clinically relevant pleiotropic effects of statins: drug properties or effects of profound cholesterol reduction?
C. Comparato (2001)
HMG CoA reductase inhibitors. In vivo effects on carotid intimal thickening in normocholesterolemic rabbits.
M. R. Soma (1993)
Inhibition of cholesterol synthesis in vitro and in vivo by ML-236A and ML-236B, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
A. Endo (1977)
Effects of fluvastatin on leukocyte-endothelial cell adhesion in hypercholesterolemic rats.
M. Kimura (1997)
Histone modification in early and late Drosophila embryos.
V. Giancotti (1984)
Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.
J. R. Downs (1998)
Stimulation of bone formation in vitro and in rodents by statins.
G. Mundy (1999)
Inhibitor of proliferation of arterial smooth-muscle cells by fluvastatin
A. Corsini (1996)
HMG-CoA reductase inhibitors: an exciting development in the treatment of hyperlipoproteinemia.
Faizulla Gulamhusein Kathawala (1991)
Non-lipid-related effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
A. Corsini (1996)
Mevalonate modulation of cell proliferation and apoptosis
R. Baetta (1997)
Antiinflammatory and Antiarteriosclerotic Actions of HMG-CoA Reductase Inhibitors in a Rat Model of Chronic Inhibition of Nitric Oxide Synthesis
W. Ni (2001)
Update on the pathogenesis of atherosclerosis.
R. Wissler (1991)
Peroxisome proliferator–activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor–deficient mice
A. Li (2000)
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 2. Structural modification of 7-(substituted aryl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives.
G. Stokker (1985)
Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation.
J. Ip (1990)
Non-lipid-related effects of statins
S. Bellosta (2000)
Alterations in the rates of synthesis and degradation of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase produced by cholestyramine and mevinolin.
P. A. Edwards (1983)
Competitive inhibition of 3‐hydroxy‐3‐methylglutaryl coenzyme a reductase by ML‐236A and ML‐236B fungal metabolites, having hypocholesterolemic activity
A. Endo (2004)
Amelioration of Angiotensin II–Induced Cardiac Injury by a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor
R. Dechend (2001)
Inhibition of isoprenoid biosynthesis induces apoptosis in human promyelocytic HL-60 cells.
D. Pérez-Sala (1994)
Simvastatin releases Ca2+ from a thapsigargin-sensitive pool and inhibits InsP3-dependent Ca2+ mobilization in vascular smooth muscle cells.
Nelson Escobales (1996)
Inhibition of endothelial cell migration by cerivastatin, an HMG‐CoA reductase inhibitor: contribution to its anti‐angiogenic effect
L. Vincent (2001)
Matrix metalloproteinases and cardiovascular disease.
C. Dollery (1995)
Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS).
J. Jukema (1995)
Inhibition of Monocyte Chemotactic Protein-1 Synthesis by Statins
M. Romano (2000)
Stimulation of anchorage independent proliferation of human adrenocortical carcinoma cells by inhibition of cholesterol biosynthesis.
D. Dunnington (1989)
Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)
H. Buchwald (1990)
Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
J. Shepherd (1995)
Statins and monocytes
U. Ikeda (1999)
Direct vascular effects of HMG-CoA reductase inhibitors.
S. Bellosta (1997)
Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors.
U. Laufs (1998)
Phosphorylation of Ser871 impairs the function of His865 of Syrian hamster 3-hydroxy-3-methylglutaryl-CoA reductase.
R. V. Omkumar (1994)
Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme
G. Gil (1985)
Regulation of Peroxisome Proliferator-Activated Receptor γ Expression by Adipocyte Differentiation and Determination Factor 1/Sterol Regulatory Element Binding Protein 1: Implications for Adipocyte Differentiation and Metabolism
L. Fajas (1999)
Simvastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia.
P. Todd (1990)
Inhibition by simvastatin, but not pravastatin, of glucose‐induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L‐type Ca2+ channels in rat islet β‐cells
T. Yada (1999)
Prenyl proteins in eukaryotic cells: a new type of membrane anchor.
J. Glomset (1990)
V. Rodwell (2000)
Simvastatin inhibits the oxidation of low-density lipoproteins by activated human monocyte-derived macrophages.
L. Giroux (1993)
Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).
J. Herd (1997)
Lovastatin inhibits low-density lipoprotein oxidation and alters its fluidity and uptake by macrophages: in vitro and in vivo studies.
M. Aviram (1992)
3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.
C. Guijarro (1998)
Differential effects of lovastatin on the trafficking of endogenous and lipoprotein-derived cholesterol in human monocyte-derived macrophages.
A. Cignarella (1998)
HMG-CoA reductase inhibitors suppress macrophage growth induced by oxidized low density lipoprotein.
M. Sakai (1997)
HMG CoA reductase inhibitors.
G. Feussner (1994)
Citrinin, an inhibitor of cholesterol synthesis.
A. Endo (1976)
Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens.
J. Kane (1990)
Antiatherothrombotic properties of statins: implications for cardiovascular event reduction.
R. Rosenson (1998)
Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells.
I. Inoue (2000)
Molecular Dissection of the Role of the Membrane Domain in the Regulated Degradation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (*)
H. Kumagai (1995)
Atorvastatin Upregulates Type III Nitric Oxide Synthase in Thrombocytes, Decreases Platelet Activation, and Protects From Cerebral Ischemia in Normocholesterolemic Mice
U. Laufs (2000)
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.
A. Tonkin (1998)
3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Inhibitors
D. Illingworth (1994)
Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevicompactum.
A. Brown (1976)
Degradation of HMG-CoA Reductase in Vitro
T. Moriyama (1998)
New insights into the pharmacodynamic and pharmacokinetic properties of statins.
A. Corsini (1999)
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.
F. McTaggart (2001)
Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes.
D. Nakai (2001)
Effect of the new HMG-CoA reductase inhibitor cerivastatin (BAY W 6228)on migration, proliferation and cholesterol synthesis in arterial myocytes.
A. Corsini (1996)
HMG-CoA reductase inhibitors reduce acetyl LDL endocytosis in mouse peritoneal macrophages.
F. Bernini (1995)
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994.
T. Pedersen (2004)
3-Hydroxy-3-methylglutaryl-coenzyme A reductase. The difference in the mechanism of the in vitro modulation by phosphorylation and dephosphorylation to modulation of enzyme activity by non-esterified cholesterol.
S. Venkatesan (1982)
The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
Yasuko Kureishi (2000)
Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N'-bis(2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells.
M. Soma (1992)
Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators.
B. Pitt (1999)
Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins.
J. Grünler (1994)
Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)
G. Watts (1992)
Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.
G. O’Driscoll (1997)
CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effect on various animal species.
Y. Tsujita (1986)
Prevention of coronary heart disease in clinical practice
K. Pyörälä (1994)
Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme.
M. Nakanishi (1988)
3-hydroxy-3-methylglutaryl coenzyme A reductase is sterol-dependently cleaved by cathepsin L-type cysteine protease in the isolated endoplasmic reticulum.
T. Moriyama (2001)
Vastatins inhibit tissue factor in cultured human macrophages. A novel mechanism of protection against atherothrombosis.
S. Colli (1997)
Simvastatin Has Anti-Inflammatory and Antiatherosclerotic Activities Independent of Plasma Cholesterol Lowering
C. Sparrow (2001)
Effects of compactin (ML-236 B) on biliary lipid composition and cholesterol catabolism in the hamster.
E. Bosisio (1982)
ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinium.
A. Endo (1976)
Biosynthesis and characterization of (S)-and (R)-3-hydroxy-3-methylglutaryl coenzyme A.
K. Bischoff (1992)
The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment.
G. Riegger (1999)
Role of the mevalonate pathway of isoprenoid synthesis in IL-8 generation by activated monocytic cells.
R. Terkeltaub (1994)
Regulation of the mevalonate pathway
J. Goldstein (1990)
Structural Mechanism for Statin Inhibition of HMG-CoA Reductase
E. Istvan (2001)
Effect of statin therapy on restenosis after coronary stent implantation.
D. Walter (2000)
Statins and the risk of dementia
H. Jick (2000)
Inhibition of 3-Hydroxy-3-methylglutaryl (HMG)-CoA Reductase Blocks Hypoxia-mediated Down-regulation of Endothelial Nitric Oxide Synthase*
U. Laufs (1997)
Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway.
P. A. Edwards (1999)
Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.
A. Alberts (1980)
Hep-G2 cells and primary rat hepatocytes differ in their response to inhibitors of HMG-CoA reductase.
M. Shaw (1990)
Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site
G. Weitz-Schmidt (2001)
Cerivastatin: pharmacology of a novel synthetic and highly active HMG-CoA reductase inhibitor.
H. Bischoff (1997)
Lovastatin modulates in vivo and in vitro the plasminogen activator/plasmin system of rat proximal tubular cells: role of geranylgeranylation and Rho proteins.
M. Essig (1998)
The role of the membrane domain in the regulated degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.
K. T. Chun (1992)
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
F. Sacks (1996)
Long-Term Effects of Pravastatin on Plasma Concentration of C-reactive Protein
P. Ridker (1999)
Crystal structure of the catalytic portion of human HMG‐CoA reductase: insights into regulation of activity and catalysis
E. Istvan (2000)
This paper is referenced by
Anti-cancer properties of " hydrophilic and hydrophobic " statins and cyclin-dependent kinases
Clifford W. Fong (2015)
Fundamental Cause Theory, Technological Innovation, and Health Disparities: The Case of Cholesterol in the Era of Statins∗
V. Chang (2009)