ArticleJournal of lipid research2009
The synergistic inhibition of atherogenesis in apoE-/- mice between pravastatin and the sPLA2 inhibitor varespladib (A-002).
Article in Journal of lipid research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 64 citations in OpenAlex.
- Prognostic utility of secretory phospholipase A(2) in patients with stable coronary artery disease.Clinical chemistry · 2011Trial
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- Unraveling snake venom phospholipase APharmacological reports : PR · 2023Review
- Racial Disparities and Cardiometabolic Risk: New Horizons of Intervention and Prevention.Current diabetes reports · 2022Review
- Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms.Acta pharmaceutica Sinica. B · 2020Article
- Varespladib Inhibits the Phospholipase ABiomedicines · 2020Article
- New quinoxalinone inhibitors targeting secreted phospholipase A2 and α-glucosidase.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect?British journal of pharmacology · 2017Review
- The Therapeutic Potential of Anti-Inflammatory Exerkines in the Treatment of Atherosclerosis.International journal of molecular sciences · 2017Review
- Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in Female ApoE Knockout Mice.The Journal of nutrition · 2015Article
- Anti-inflammatory therapies for atherosclerosis.Nature reviews. Cardiology · 2015Review
- Matrix metalloproteinase-2 negatively regulates cardiac secreted phospholipase A2 to modulate inflammation and fever.Journal of the American Heart Association · 2015Article
- Acute coronary syndromes: targeting inflammation-what has the VISTA-16 trial taught us?Nature reviews. Cardiology · 2014Article
- Article
- The human paraoxonase gene cluster as a target in the treatment of atherosclerosis.Antioxidants & redox signaling · 2012Review
- Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention.Chemical reviews · 2011Review
- Secreted phospholipase A2, lipoprotein hydrolysis, and atherosclerosis: integration with lipidomics.Analytical and bioanalytical chemistry · 2011Review
- Anti-inflammatory therapeutics for the treatment of atherosclerosis.Nature reviews. Drug discovery · 2011Review
- Secretory phospholipase A2: a multifaceted family of proatherogenic enzymes.Current cardiology reports · 2009Review
- The capacity of group V sPLA2 to increase atherogenicity of ApoE-/- and LDLR-/- mouse LDL in vitro predicts its atherogenic role in vivo.Arteriosclerosis, thrombosis, and vascular biology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Secretory phospholipase A2 (sPLA2) activity promotes foam cell formation, increases proinflammatory bioactive lipid levels, decreases HDL levels, increases atherosclerosis in transgenic mice, and is an independent marker of cardiovascular disease. The effects of the sPLA2 inhibitor A-002 (varespladib) and pravastatin as monotherapies and in combination on atherosclerosis, lipids, and paraoxonase (PON) activity in apoE(-/-) mice were investigated. Male apoE(-/-) mice were placed on a 12-week high-fat diet supplemented with A-002 alone or combined with pravastatin. Atherosclerotic lesions were examined for size and composition using en face analysis, Movat staining, anti-CD68, and anti-alpha actin antibodies. Plasma lipids and PON activity were measured. A-002 decreased atherosclerotic lesion area by approximately 75% while increasing fibrous cap size by over 200%. HDL levels increased 40% and plasma PON activity increased 80%. Pravastatin monotherapy had no effect on lesion size but when combined with A-002, decreased lesion area 50% and total cholesterol levels 18% more than A-002 alone. A-002, a sPLA2 inhibitor, acts synergistically with pravastatin to decrease atherosclerosis, possibly through decreased levels of systemic inflammation or decreased lipid levels. A-002 treatment also resulted in a profound increase in plasma PON activity and significantly larger fibrous caps, suggesting the formation of more stable plaque architecture.
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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.