ArticleThe Journal of clinical investigation2011
Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 108 citations in OpenAlex.
- Review
- The multidrug resistance protein inhibitor, MK571 inhibits the hypercontractility state in prostate from obese mice.World journal of urology · 2025Article
- Structural basis of human ABCC4 recognition of cAMP and ligand recognition flexibility.Cell & bioscience · 2025Article
- Metabolomic analysis reveals an important role of sphingosine 1-phosphate in the development of HFMD due to EV-A71 infection.Antimicrobial agents and chemotherapy · 2025Article
- Long-Term Adverse Effects of Perinatal Hypoxia on the Adult Pulmonary Circulation Vary Between Males and Females in a Murine Model.Physiological research · 2024Article
- Fetal sex and the relative reactivity of human umbilical vein and arteries are key determinants in potential beneficial effects of phosphodiesterase inhibitors.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- Structural basis of prostaglandin efflux by MRP4.Nature structural & molecular biology · 2024Article
- Article
- Mesenchymal stem cell-derived extracellular vesicles prevent the formation of pulmonary arterial hypertension through a microRNA-200b-dependent mechanism.Respiratory research · 2023Article
- PARM1 Drives Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension via AKT/FOXO3A Axis.International journal of molecular sciences · 2023Article
- Multidrug-resistant protein inhibitor and phosphodiesterase inhibitor potentiate the vasodilator effect induced by photobiomodulation in isolated aortic rings.Lasers in medical science · 2022Article
- Phosphodiesterase 4D promotes angiotensin II-induced hypertension in mice via smooth muscle cell contraction.Communications biology · 2022Article
- Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension.Science advances · 2021Article
- Combination Therapy with STAT3 Inhibitor Enhances SERCA2a-Induced BMPR2 Expression and Inhibits Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Article
- Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas.Antioxidants (Basel, Switzerland) · 2021Article
- Multidrug resistance-associated protein 4 (Mrp4) is a novel genetic factor in the pathogenesis of obesity and diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Article
- Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness.Scientific reports · 2020Article
- A novel secreted-cAMP pathway inhibits pulmonary hypertension via a feed-forward mechanism.Cardiovascular research · 2020Article
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 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance-associated protein 4 (MRP4, also known as Abcc4) regulates intracellular levels of cAMP and cGMP in arterial SMCs. Here, we report our studies of the role of MRP4 in the development and progression of pulmonary arterial hypertension (PAH), a severe vascular disease characterized by chronically elevated pulmonary artery pressure and accompanied by remodeling of the small pulmonary arteries as a prelude to right heart failure and premature death. MRP4 expression was increased in pulmonary arteries from patients with idiopathic PAH as well as in WT mice exposed to hypoxic conditions. Consistent with a pathogenic role for MRP4 in PAH, WT mice exposed to hypoxia for 3 weeks showed reversal of hypoxic pulmonary hypertension (PH) following oral administration of the MRP4 inhibitor MK571, and Mrp4-/- mice were protected from hypoxic PH. Inhibition of MRP4 in vitro was accompanied by increased intracellular cAMP and cGMP levels and PKA and PKG activities, implicating cyclic nucleotide-related signaling pathways in the mechanism underlying the protective effects of MRP4 inhibition. Our data suggest that MRP4 could represent a potential target for therapeutic intervention in PAH.
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.