Essential fatty acids as possible mediators of the actions of statins
Prostaglandins Leukotrienes and Essential Fatty AcidsPublished 1 July 2001
Undurti N. Das
Citations77
SJR quartileQ2
SJR score0.86
SNIP0.76
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
It is suggested that essential fatty acids and their metabolites may serve as second messengers of the actions of statins.
Abstract
Statins and polyunsaturated fatty acids have similar actions: both enhance endothelial nitric oxide synthesis, inhibit the production of pro-inflammatory cytokines, lower cholesterol levels, prevent atherosclerosis and are of benefit in coronary heart disease, stroke and osteoporosis. Statins enhance the conversion of linoleic acid and eicosapentaenoic acid to their long chain derivatives. Animals with essential fatty acid deficiency show an increase in HMG-CoA reductase activity, which reverts to normalcy following topical application of linoleic acid. Similarly to statins, polyunsaturated fatty acids also inhibit HMG-CoA reductase activity. In view of the similarity in their actions and as statins influence essential fatty acid metabolism, it is suggested that essential fatty acids and their metabolites may serve as second messengers of the actions of statins.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
New England Journal of MedicineThe Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholesterol Levels
7,491 Citations1996Frank M. Sacks, Marc A. Pfeffer +10 more
It is demonstrated that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels and was also greater in patients with higher pretreatment levels of LDL cholesterol.
NatureRegulation of the mevalonate pathway
5,411 Citations1990J GOLDSTEIN, Michael S. Brown
The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control, and could be useful in treating certain forms of cancer as well as heart disease.
The LancetDietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial
3,803 Citations1999
Dietary supplementation with n-3 PUFA led to a clinically important and statistically significant benefit and vitamin E had no benefit and its effects on fatal cardiovascular events require further exploration.
ScienceStimulation of Bone Formation in Vitro and in Rodents by Statins
1,779 Citations1999Gregory R. Mundy, R.J. Burriss Garrett +7 more
It is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents, and may have therapeutic applications for the treatment of osteoporosis.
The LancetStatins and the risk of dementia
1,767 Citations2000Hershel Jick, GL Zornberg +3 more
Individuals of 50 years and older who were prescribed statins had a substantially lowered risk of developing dementia, independent of the presence or absence of untreated hyperlipidaemia, or exposure to nonstatin LLAs.
Nature MedicineThe HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.
1,429 Citations2000Yasuko Kureishi, Zhengyu Luo +6 more
Simvastatin enhanced phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase, inhibited apoptosis and accelerated vascular structure formation in vitro in an Akt-dependent manner, and promoted angiogenesis in ischemic limbs of normocholesterolemic rabbits.
The EMBO JournalPolyunsaturated fatty acids are potent neuroprotectors
484 Citations2000Inger Lauritzen, Nicolas Blondeau +4 more
The data suggest that the opening of background K+ channels, like TREK‐1 and TRAAK, which are activated by arachidonic acid and other polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor in this neuroprotective effect.
The LancetInhibition of proinflammatory cytokine production by pravastatin
373 Citations1999Robert S. Rosenson, Christy Tangney +1 more
The LancetOral statins and increased bone-mineral density in postmenopausal women
328 Citations2000CJ Edwards, D.J. Hart +1 more
A significant increase of bone-mineral density associated with taking statins in postmenopausal women is reported, suggesting that the cholesterol-lowering drugs statins increase bone formation.
CirculationSimvastatin Preserves the Ischemic-Reperfused Myocardium in Normocholesterolemic Rat Hearts
327 Citations1999Allan M. Lefer, Barry J. Campbell +4 more
Evidence is provided that HMG-CoA reductase inhibitors are potent and effective cardioprotective agents that inhibit leukocyte-endothelial cell interactions and preserve cardiac contractile function and coronary perfusion after myocardial ischemia and reperfusion.
Proceedings of the National Academy of SciencesHippocampal acetylcholine release during memory testing in rats: augmentation by glucose.
316 Citations1996Michael E. Ragozzino, Katharine Unick +1 more
The findings suggest that glucose may enhance memory by directly or indirectly increasing the release of ACh, and indicate that hippocampal ACh release is increased in rats performing a spatial task.
Laboratory InvestigationInhibition of Monocyte Chemotactic Protein-1 Synthesis by Statins
299 Citations2000Maria Rosaria Romano, Luisa Diomede +12 more
Journal of Biological ChemistryInhibition of Neuronal Apoptosis by Docosahexaenoic Acid (22:6n-3)
295 Citations2000Hee‐Yong Kim, Mohammed Akbar +2 more
Collectively, enrichment of neuronal cells with 22:6n-3 increases the PS content and Raf-1 translocation, down-regulates caspase-3 activity, and prevents apoptotic cell death, strongly suggesting that the protective effect of 22: 6n- 3 may be mediated at least in part through the promoted accumulation of PS in neuronal membranes.
Prostaglandins Leukotrienes and Essential Fatty AcidsBeneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?
235 Citations2000Undurti N. Das
There appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids which may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
ScienceInduction and Maintenance of the Neuronal Cholinergic Phenotype in the Central Nervous System by BMP-9
225 Citations2000Ignacio López-Coviella, Brygida Berse +3 more
In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylCholine transporter and up-regulated acetylcholine synthesis and these data indicate that B MP-9 is a differentiating factor for cholinerential central nervous system neurons.
The LancetEffect of statins on C-reactive protein in patients with coronary artery disease
210 Citations1999Timo Strandberg, Hannu Vanhanen +1 more
The view that the autoimmune response in LEMS retards tumour growth and the recognition of LEMS in any patients with SCLC could have important implications for long-term outcome after antitumour therapy is supported.
DiabetologiaDietary fish oil augments nitric oxide production or release in patients with Type 2 (non-insulin-dependent) diabetes mellitus
194 Citations1993Gary E. McVeigh, G. Brennan +6 more
Cancer LettersTumoricidal action of cis-unsaturated fatty acids and their relationship to free radicals and lipid peroxidation
175 Citations1991Undurti N. Das
The results suggest that c-UFA-induced tumoricidal action is a free radical dependent process and that there are significant differences between normal and tumor cells in fatty acid uptake and distribution.
Proceedings of the National Academy of SciencesModulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.
163 Citations1993Shlomo Yehuda, R Carasso
The effects of preparations containing different ratios of highly purified free alpha-linolenic acid to linoleic acid on learning performance, pain thresholds, and thermoregulatory control of d-amphetamine-induced hypothermia during 4 weeks of treatment are examined.
Prostaglandins Leukotrienes and Essential Fatty AcidsEssential fatty acids, lipid peroxidation and apoptosis
161 Citations1999Undurti N. Das
It is suggested that long-chain fatty acids induce apoptosis by enhancing lipid peroxidation, suppressing BCL-2 expression possibly by phosphorylation and augmentation of P450 activity, and may, infact act at the level of gene/oncogene expression in producing their cytotoxic action on tumour cells.
Pharmacology Biochemistry and BehaviorDietary Docosahexaenoic Acid Increases Cerebral Acetylcholine Levels and Improves Passive Avoidance Performance in Stroke-Prone Spontaneously Hypertensive Rats
140 Citations1997Masaru Minami, Shin‐ichi Kimura +10 more
The results suggest that cholinergic dysfunction in the brain of control SHRSP is responsible, at least in part, for the impaired learning ability and the dietary DHA ameliorates this performance failure.
Biochemical and Biophysical Research CommunicationsPolyunsaturated fatty acids augment free radical generation in tumor cells in vitro
136 Citations1987Undurti N. Das, M.E. Bégin +3 more
Results suggested that linoleate (LA), gamma-linolenate (GLA), arachidonate (AA) and eicosapentaenoate (EPA) can enhance nitroblue tetrazolium reduction in tumor cells but not in normal cells, indicating that PUFA induced growth inhibition and cytotoxicity to tumor cells may be due to enhanced free radical generation.
Proceedings of the National Academy of SciencesArachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.
117 Citations1993Naichen Yu, Jean‐Luc Martin +2 more
The effects of NE reported here further stress the notion that certain neurotransmitters may play a role in the regulation of energy metabolism in the cerebral cortex and point at astrocytes as the likely targets of such metabolic effects.
Prostaglandins Leukotrienes and Essential Fatty AcidsEffect of prostaglandins and their precursors on the proliferation of human lymphocytes and their secretion of tumor necrosis factor and various interleukins
115 Citations1994G. Sravan Kumar, Undurti N. Das
Data is presented which suggests that PGs including thromboxane B2 (TXB2) and their precursors such as dihomo-gamma linolenic acid (DGLA), arachidonic acid (AA) and eicosapentaenoic Acid (EPA) can inhibit T-cell proliferation and influence their ability to secrete IL-2,IL-4, IL-6 and TNF in vitro.
Thrombosis ResearchEffects of a fish oil supplement on platelet function, haemostatic variables and albuminuria in insulin-dependent diabetics
114 Citations1986Andy Haines, T. A. B. Sanders +6 more
There was a significant reduction in thromboxane production by platelets stimulated by collagen in vitro in the group who took the fish oil supplement and the lag phase before aggregation was prolonged.
Cancer LettersLocal application of γ-linolenic acid in the treatment of human gliomas
111 Citations1995Undurti N. Das, Vannemreddy Prasad +1 more
It is suggested that GLA is a safe anti-tumour agent and recommend its use in the management of human gliomas and in 15 patients with malignant glioma.
AtherosclerosisEffect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured human endothelial cells
109 Citations2000Sophie Lopez, Franck Peiretti +3 more
Results show that statins favorably modulate the expression of fibrinolytic factors produced by human endothelial cells, including tumor necrosis factor alpha and interleukin 1alpha.
Journal of Internal MedicineEffects of Simvastatin and omega‐3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia
103 Citations1998Nordøy, Bønaa +6 more
Effect of Simvastatin and omega‐3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidemia is studied.
Prostaglandins Leukotrienes and Essential Fatty AcidsBeneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network
92 Citations1994Undurti N. Das
Oral supplementation of EPA and DHA induced prolonged remission of SLE in 10 consecutive patients without any side-effects suggest that n-3 fatty acids, EPA andDHA, are useful in the management of Sle and possibly, other similar collagen vascular diseases.
Arteriosclerosis Thrombosis and Vascular BiologyEffect of ω-3 Fatty Acids and Simvastatin on Hemostatic Risk Factors and Postprandial Hyperlipemia in Patients With Combined Hyperlipemia
90 Citations2000Arne Nordøy, Kaare Harald Bønaa +3 more
Free Radical Biology and MedicineUptake and distribution of cis-unsaturated fatty acids and their effect on free radical generation in normal and tumor cells in vitro
85 Citations1987Undurti N. Das, Yung-S. Huang +3 more
The results suggest that there are significant differences between normal and tumor cells in fatty acid uptake and distribution, and in the ability of fatty acids to generate free radicals.
Journal of Lipid ResearchEffect of dietary n-3 fatty acids on HMG-CoA reductase and ACAT activities in liver and intestine of the rabbit.
80 Citations1986F. Jeffrey Field, E Albright +1 more
Lipid analysis of hepatic and intestinal microsomes demonstrated an enrichment of n-3 polyunsaturated fatty acids in membranes from rabbits ingesting the menhaden oil.
Journal of Investigative DermatologyEpidermal HMG CoA Reductase Activity in Essential Fatty Acid Deficiency: Barrier Requirements Rather Than Eicosanoid Generation Regulate Cholesterol Synthesis
66 Citations1992Ehrhardt Proksch, Kenneth R. Feingold +1 more
Barrier function modulates HMG CoA reductase activity; reduction of cholesterol synthesis with occlusion results in a further deterioration in barrier function, suggesting that increased synthesis is a protective homeostatic response; and the barrier abnormality reflects a requirement for specific fatty acids for the barrier rather than resulting from epidermal hyperplasia or decreased prostaglandin generation.
PubMedOmega-3 polyunsaturated fatty acids augment endothelium-dependent vasorelaxation by enhanced release of EDRF and vasodilator prostaglandins.
64 Citations1991D. L. Lawson, Jawahar L. Mehta +3 more
Evaluating the direct in vitro effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) on vascular reactivity in isolated rat aortic rings found that dietary supplementation with fish oil results in augmentation of endothelium-dependent vasorelaxation in experimental animals.
Nature MedicineStatins: lower lipids and better bones?
57 Citations2000Michael J. Rogers
Although statins are widely used as cholesterol-lowering drugs, a recent study suggests that these compounds have anabolic effects on bone and could be developed into new treatments for common metabolic bone diseases such as osteoporosis.
Journal of Lipid ResearchEffects of simvastatin on the metabolism of polyunsaturated fatty acids and on glycerolipid, cholesterol, and de novo lipid synthesis in THP-1 cells
50 Citations1997Patrizia Risé, Claudio Colombo +1 more
The data indicate that HMG-CoA inhibitors have profound effects on PUFA metabolism, and that the pathways for cholesterol and PUFA synthesis are mutually modulated.
PubMedRegulation of mevalonate synthesis in rat mammary glands by dietary n-3 and n-6 polyunsaturated fatty acids.
47 Citations1997Ahmed El‐Sohemy, Michael C. Archer
The mevalonate pathway may be a mechanism through which different types of dietary fat modulate breast cancer development, and the concomitant decrease in serum cholesterol and mammary gland HMG-CoA reductase levels suggests that changes in circulating cholesterol levels do not solely determine the activity of extrahepatic reduct enzyme.
Progress in Lipid ResearchAtherosclerosis: An intracellular deficiency in essential fatty acids
42 Citations1981David G. Cornwell, Rao V. Panganamala
Essential fatty acids are shunted into an intracellular cholesteryl ester pool when the endothelium is injured and the consequences are enormous; smooth muscle cells proliferate and the atherosclerotic lesion develops.
BMJFish oils and cardiovascular disease
34 Citations1995B. N. C. Prichard, Christopher Smith +2 more
In healthy subjects increased consumption of long chain n-3 fatty acids is associated with falls in serum concentrations of triglycerides and very low density lipoprotein, and suggested mechanisms for this cardioprotective effect focused first on serum lipids.
Comparative Biochemistry and Physiology Part A Molecular & Integrative PhysiologyEffects of dietary alpha- or gamma-linolenic acid on levels and fatty acid compositions of serum and hepatic lipids, and activity and mRNA abundance of 3-hydroxy-3-methylglutaryl CoA reductase in rats
26 Citations1999Miyuki Ihara-Watanabe, Hayato Umekawa +2 more
The present results indicate that alpha-linolenic acid exhibits a larger hypocholesterolemic effect than gamma-linoleic acid, and it may be displayed mainly through the repression of the activity and mRNA expression of HMG-CoA reductase.
Advances in experimental medicine and biologyModulation of Intracellular Second Messengers by Dietary Fat during Colonic Tumor Development
17 Citations1997Robert S. Chapkin, Yi-Hai Jiang +2 more
Dietary n-3 polyunsaturated fatty acids found in fish oil are capable of suppressing carcinogen-induced ras activation in the colon prior to overt neoplasia, preventing the persistent activation and chronic down-regulation of PKC isozymes, thereby maintaining tissue PKC levels.
PubMedHMG-CoA reductase activity in the liver of rats with hereditary hypertriglyceridemia: effect of dietary fish oil.
13 Citations1994M Hromadová, E Seböková +1 more
The results of the study demonstrated that the hypocholesterolemic effect of FO added to the diet was mediated under certain conditions, by affecting of HMG-CoA reductase activity and not only by its effect on specific receptors as demonstrated before.