ArticleThe Journal of clinical investigation2001
Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
99 citing papers in PubMed, 418 citations in OpenAlex.
- Potent and selective PPAR-alpha agonist LY518674 upregulates both ApoA-I production and catabolism in human subjects with the metabolic syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2009Trial
- Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2008Trial
- Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome.Diabetes care · 2008Trial
- Dose-dependent regulation of high-density lipoprotein metabolism with rosuvastatin in the metabolic syndrome.The Journal of clinical endocrinology and metabolism · 2008Trial
- Immunometabolic reprogramming in multiple sclerosis: from pathogenic amplifier to therapeutic target in neuroinflammation and remyelination.Inflammopharmacology · 2026Review
- Plasma apolipoprotein A-I is a causal protective factor in sepsis.Scientific reports · 2025Article
- Impact of statin therapy on CD40:CD40L signaling: mechanistic insights and therapeutic opportunities.Pharmacological reports : PR · 2025Review
- TLR4 modulates simvastatin's impact on HDL cholesterol and glycemic control.Frontiers in pharmacology · 2025Article
- Induction of resistance to neurotrophic tropomyosin-receptor kinase inhibitors by HMGCS2 via a mevalonate pathway.Cancer medicine · 2024Article
- Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review.Nutrients · 2023Review
- The effects of simvastatin and fenofibrate on malondialdehyde and reduced glutathione concentrations in the plasma, liver, and brain of normolipidaemic and hyperlipidaemic rats.Arhiv za higijenu rada i toksikologiju · 2023Article
- Pharmacological Utility of PPAR Modulation for Angiogenesis in Cardiovascular Disease.International journal of molecular sciences · 2023Review
- Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Potential Therapeutic Agents That Target ATP Binding Cassette A1 (ABCA1) Gene Expression.Drugs · 2022Review
- Effects of Individual Amino Acids on PPARα Transactivation, mTORC1 Activation, ApoA-I Transcription and pro-ApoA-I Secretion.International journal of molecular sciences · 2022Article
- Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Anti-inflammatory Effects of Statins in Lung Vascular Pathology: From Basic Science to Clinical Trials.Advances in experimental medicine and biology · 2021Article
- Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells.International journal of molecular sciences · 2020Article
- Short-Chain Fatty Acids (Except Hexanoic Acid) Lower NF-kB Transactivation, Which Rescues Inflammation-Induced Decreased Apolipoprotein A-I Transcription in HepG2 Cells.International journal of molecular sciences · 2020Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statins are inhibitors of the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In addition to reducing LDL cholesterol, statin treatment increases the levels of the antiatherogenic HDL and its major apolipoprotein apoA-I. Here, we investigated the molecular mechanisms of apoA-I regulation by statins. Treatment with statins increased apoA-I mRNA levels in human HepG2 hepatoma cells, and this effect was reversed by the addition of mevalonate, implicating HMG-CoA reductase as the relevant target of these drugs. Pretreatment with Actinomycin D abolished the increase of apoA-I mRNA, indicating that statins act at the transcriptional level. Indeed, statins increased the human apoA-I promoter activity in transfected cells, and we have identified a statin response element that coincides with a PPARalpha response element known to confer fibrate responsiveness to this gene. The statin effect could be abolished not only by mevalonate, but also by geranylgeranyl pyrophosphate, whereas inhibition of geranylgeranyl transferase activity or treatment with an inhibitor of the Rho GTP-binding protein family increased PPARalpha activity. Using dominant negative forms of these proteins, we found that Rho A itself mediates this response. Because cotreatment with statins and fibrates activated PPARalpha in a synergistic manner, these observations provide a molecular basis for combination treatment with statins and fibrates in coronary heart disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.