ArticleBritish journal of pharmacology2015
Serelaxin-mediated signal transduction in human vascular cells: bell-shaped concentration-response curves reflect differential coupling to G proteins.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 38 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
38 citing papers in PubMed, 72 citations in OpenAlex.
- Vascular effects of serelaxin in patients with stable coronary artery disease: a randomized placebo-controlled trial.Cardiovascular research · 2021Trial
- Impact and Interrelationships of Striatal Proteins, EPHB2, OPRM1, and PER2 on Mild Cognitive Impairment.Molecular neurobiology · 2025Article
- Role of Relaxin Signaling in Cancer: A Review.Biochemical pharmacology · 2024Review
- Engineering a long acting, non-biased relaxin agonist using Protein-in-Protein technology.Biochemical pharmacology · 2024Article
- Development of Novel High-Affinity Antagonists for the Relaxin Family Peptide Receptor 1.ACS pharmacology & translational science · 2023Article
- Relaxin in fibrotic ligament diseases: Its regulatory role and mechanism.Frontiers in cell and developmental biology · 2023Review
- Characterization of a new potent and long-lasting single chain peptide agonist of RXFP1 in cells and in vivo translational models.Scientific reports · 2022Article
- Relaxin Inhibits the Cardiac Myofibroblast NLRP3 Inflammasome as Part of Its Anti-Fibrotic Actions via the Angiotensin Type 2 and ATP (P2X7) Receptors.International journal of molecular sciences · 2022Article
- Enhancing the Therapeutic Potential of Mesenchymal Stromal Cell-Based Therapies with an Anti-Fibrotic Agent for the Treatment of Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- Ligand-activated RXFP1 gene therapy ameliorates pressure overload-induced cardiac dysfunction.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice.Journal of the American Heart Association · 2020Article
- Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model.International journal of molecular sciences · 2020Article
- Relaxin Can Mediate Its Anti-Fibrotic Effects by Targeting the Myofibroblast NLRP3 Inflammasome at the Level of Caspase-1.Frontiers in pharmacology · 2020Article
- AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis.Journal of the American Society of Nephrology : JASN · 2019Article
- Targeting the relaxin/insulin-like family peptide receptor 1 and 2 with small molecule compounds.Molecular and cellular endocrinology · 2019Review
- Relaxin and extracellular matrix remodeling: Mechanisms and signaling pathways.Molecular and cellular endocrinology · 2019Review
- Absent or Excessive Corpus Luteum Number Is Associated With Altered Maternal Vascular Health in Early Pregnancy.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Real-time examination of cAMP activity at relaxin family peptide receptors using a BRET-based biosensor.Pharmacology research & perspectives · 2018Article
- Heart Disease and Relaxin: New Actions for an Old Hormone.Trends in endocrinology and metabolism: TEM · 2018Review
- The Vasculature in Prediabetes.Circulation research · 2018Review
Corrections and comments
- Expression of concern
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIn a recently conducted phase III clinical trial, RELAX-AHF, serelaxin infusion over 48 h improved short- and long-term clinical outcomes in patients with acute heart failure. In this study we used human primary cells from the umbilical vasculature to better understand the signalling mechanisms activated by serelaxin. EXPERIMENTAL APPROACH: We examined the acute effects of serelaxin on signal transduction mechanisms in primary human umbilical vascular cells and its chronic actions on markers of cardiovascular function and disease. KEY
resultsThe RXFP1 receptor, the cognate serelaxin receptor, was expressed at the cell surface in HUVECs and human umbilical vein smooth muscle cells (HUVSMCs), human umbilical artery smooth muscle cells (HUASMCs) and human cardiac fibroblasts (HCFs), but not human umbilical artery endothelial cells. In HUVECs and HUVSMCs, serelaxin increased cAMP, cGMP accumulation and pERK1/2, and the concentration-response curves (CRCs) were bell-shaped. Similar bell-shaped CRCs for cGMP and pERK1/2 were observed in HCFs, whereas in HUASMCs, serelaxin increased cAMP, cGMP and pERK1/2 with sigmoidal CRCs. Gαi/o and lipid raft disruption, but not Gαs inhibition, altered the serelaxin CRC for cAMP and cGMP accumulation in HUVSMC but not HUASMC. Longer term serelaxin exposure increased the expression of neuronal NOS, VEGF, ETβ receptors and MMPs (gelatinases) in RXFP1 receptor-expressing cells. CONCLUSIONS AND IMPLICATIONS: Serelaxin caused acute and chronic changes in human umbilical vascular cells that were cell background dependent. Bell-shaped CRCs that were observed only in venous cells and fibroblasts involved Gαi/o located within membrane lipid rafts.
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.