APJ, a G-protein coupled receptor, regulates coronary angiogenesis in the developing mouse heart. However, the exact mechanism by which APJ regulates coronary angiogenesis from its dual ligands, ELABELA and APELIN, is unclear. Our study show that ELABELA and APELIN both stimulate angiogenic activities such as proliferation and sprouting outgrowth in explant cultures. We found APELIN to be a more robust angiogenic stimulant compared to ELABELA. When explant cultures were stimulated by both ligands together, we found that ELABELA repress the angiogenic activity of APELIN. Collectively, we show that ELABELA and APELIN regulate coronary angiogenesis in a competitive manner.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10550380 | PMC |
http://dx.doi.org/10.17912/micropub.biology.000886 | DOI Listing |
Nat Commun
December 2024
Experimental Medicine & Immunotherapeutics, University of Cambridge, Cambridge, UK.
We describe a structural and functional study of the G protein-coupled apelin receptor, which binds two endogenous peptide ligands, apelin and Elabela/Toddler (ELA), to regulate cardiovascular development and function. Characterisation of naturally occurring apelin receptor variants from the UK Genomics England 100,000 Genomes Project, and AlphaFold2 modelling, identifies T89 as important in the ELA binding site, and R168 as forming extensive interactions with the C-termini of both peptides. Base editing to introduce an R/H168 variant into human stem cell-derived cardiomyocytes demonstrates that this residue is critical for receptor binding and function.
View Article and Find Full Text PDFBiomedicines
November 2024
Division of Medical Biology, Faculty of Nursing and Midwifery, Wroclaw Medical University, 50-368 Wrocław, Poland.
: SARS-CoV-2 enters cells primarily by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, thereby blocking its physiological functions, affecting the apelinergic system, and inhibiting the cleavage of its peptides. The appropriate concentration of peptides in the apelinergic system influences the maintenance of homeostasis and protects against cardiovascular diseases. In our research, we determined the level of selected parameters of the apelinergic system-apelin (AP), elabela (ELA), and the apelin receptor (APJ)-in repeat blood donors.
View Article and Find Full Text PDFBiochem J
December 2024
Department of Biotechnology, Bhupat and Jyoti Mehta School of Biological Sciences, Indian Institute of Technology Madras, Chennai, India.
G protein-coupled receptors (GPCRs) serve as critical communication hubs, translating a wide range of extracellular signals into intracellular responses that govern numerous physiological processes. In class-A GPCRs, conserved motifs mediate conformational changes of the active states of the receptor, and signal transduction is achieved by selectively binding to Gα proteins and/or adapter protein, arrestin. Apelin receptor (APJR) is a class-A GPCR that regulates a wide range of intracellular signalling cascades in response to apelin and elabela peptide ligands.
View Article and Find Full Text PDFHippokratia
January 2023
Department of Cardiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.
Background: Elabela/toddler (ELA-32) is a recently identified endogenous apelin receptor ligand. ELA levels are known to rise in heart failure (HF) patients. However, the association between elevated ELA levels and prognosis in these patients remains unknown.
View Article and Find Full Text PDFLife Sci
November 2024
Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India. Electronic address:
Acute kidney injury (AKI) has emerged as a global health crisis, surpassing mortality rates associated with several cancers and heart failure. The lack of effective therapies, coupled with challenges in diagnosis and the high cost of kidney transplantation, underscores the urgent need to explore novel therapeutic targets and strategies for AKI. Understanding the intricate pathophysiology of AKI is paramount in this endeavor.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!