ArticleTheoretical biology & medical modelling2006
Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b.
Article in Theoretical biology & medical modelling, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 167 citations in OpenAlex.
- Comparative Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Response to a Physical Activity Intervention in Older Adults: Results From the Lifestyle Interventions and Independence for Elders Study.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Trial
- 24-hour and nighttime blood pressures in type 2 diabetic hypertensive patients following morning or evening administration of olmesartan.Journal of clinical hypertension (Greenwich, Conn.) · 2009Trial
- Chemokine-Receptor Modulation Shapes Neuroinflammatory and Biomechanical Responses in Organotypic Hippocampal Cultures After Oxygen-Glucose Deprivation.ACS chemical neuroscience · 2026Article
- Beyond VDR: Vitamin D Metabolism Genes in Tuberculosis Susceptibility, Immune Response and Implications for Diabetes Mellitus.Infection and drug resistance · 2026Review
- Immunomodulation and immunopharmacology in heart failure.Nature reviews. Cardiology · 2024Review
- Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway.Scientific reports · 2021Article
- Infiltrating CCR2Scientific reports · 2019Article
- The Angiotensin Receptor Blocker Losartan Suppresses Growth of Pulmonary Metastases via AT1R-Independent Inhibition of CCR2 Signaling and Monocyte Recruitment.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Recent advances in the treatment of pathogenic infections using antibiotics and nano-drug delivery vehicles.Drug design, development and therapy · 2019Review
- Inhibitory Effects of Angiotensin II Receptor Blockade on Human Tenon Fibroblast Migration and Reactive Oxygen Species Production in Cell Culture.Translational vision science & technology · 2018Article
- Sprue-Like Enteropathy Associated With Oxcarbazepine.The American journal of gastroenterology · 2016Article
- A Dormant Microbial Component in the Development of Preeclampsia.Frontiers in medicine · 2016Review
- AT1R blockade in adverse milieus: role of SMRT and corepressor complexes.American journal of physiology. Renal physiology · 2015Article
- Inflammation and vitamin D: the infection connection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2014Review
- Effect of candesartan on the expression of sclera-choroidal intercellular adhesion molecule-1 in hypercholesterolemic models.Clinics (Sao Paulo, Brazil) · 2014Article
- Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.PloS one · 2014Article
- Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders.Clinical science (London, England : 1979) · 2012Review
- Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes.Cardiovascular diabetology · 2012Article
- Binding site characterization of G protein-coupled receptor by alanine-scanning mutagenesis using molecular dynamics and binding free energy approach: application to C-C chemokine receptor-2 (CCR2).Molecular diversity · 2012Article
- Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study.Cardiovascular diabetology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere have been indications that common Angiotensin Receptor Blockers (ARBs) may be exerting anti-inflammatory actions by directly modulating the immune system. We decided to use molecular modelling to rapidly assess which of the potential targets might justify the expense of detailed laboratory validation. We first studied the VDR nuclear receptor, which is activated by the secosteroid hormone 1,25-dihydroxyvitamin-D. This receptor mediates the expression of regulators as ubiquitous as GnRH (Gonadatrophin hormone releasing hormone) and the Parathyroid Hormone (PTH). Additionally we examined Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma), which affects the function of phagocytic cells, and the C-CChemokine Receptor, type 2b, (CCR2b), which recruits monocytes to the site of inflammatory immune challenge.
resultsTelmisartan was predicted to strongly antagonize (Ki asymptotically equal to 0.04 nmol) the VDR. The ARBs Olmesartan, Irbesartan and Valsartan (Ki asymptotically equal to10 nmol) are likely to be useful VDR antagonists at typical in-vivo concentrations. Candesartan (Ki asymptotically equal to 30 nmol) and Losartan (Ki asymptotically equal to 70 nmol) may also usefully inhibit the VDR. Telmisartan is a strong modulator of PPARgamma (Ki asymptotically equal to 0.3 nmol), while Losartan (Ki asymptotically equal to 3 nmol), Irbesartan (Ki asymptotically equal to 6 nmol), Olmesartan and Valsartan (Ki asymptotically equal to 12 nmol) also seem likely to have significant PPAR modulatory activity. Olmesartan and Irbesartan (Ki asymptotically equal to 9 nmol) additionally act as antagonists of a theoretical model of CCR2b. Initial validation of this CCR2b model was performed, and a proposed model for the Angiotensin II Type1 receptor (AT2R1) has been presented.
conclusionMolecular modeling has proven valuable to generate testable hypotheses concerning receptor/ligand binding and is an important tool in drug design. ARBs were designed to act as antagonists for AT2R1, and it was not surprising to discover their affinity for the structurally similar CCR2b. However, this study also found evidence that ARBs modulate the activation of two key nuclear receptors-VDR and PPARgamma. If our simulations are confirmed by experiment, it is possible that ARBs may become useful as potent anti-inflammatory agents, in addition to their current indication as cardiovascular drugs.
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.