ArticlePloS one2019
2-Cl-C.OXT-A stimulates contraction through the suppression of phosphodiesterase activity in human induced pluripotent stem cell-derived cardiac organoids.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 27 citations in OpenAlex.
- Response of human iPSC-cardiomyocytes to adrenergic drugs assessed by high-throughput pericellular oxygen measurements and computational modeling.Journal of molecular and cellular cardiology plus · 2026Article
- Review
- Spatiotemporal profiling of protein kinase A activity in spontaneously beating hiPSC-derived cardiac organoids.iScience · 2025Article
- Revolutionizing cardiovascular research: Human organoids as a Beacon of hope for understanding and treating cardiovascular diseases.Materials today. Bio · 2025Review
- Vascularised cardiac spheroids-on-a-chip for testing the toxicity of therapeutics.Scientific reports · 2024Article
- Promises and challenges of cardiac organoids.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Advances in 3D Organoid Models for Stem Cell-Based Cardiac Regeneration.International journal of molecular sciences · 2023Review
- Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering.Circulation research · 2023Review
- Vascularized Tissue Organoids.Bioengineering (Basel, Switzerland) · 2023Review
- Cardiac Organoids: A 3D Technology for Modeling Heart Development and Disease.Stem cell reviews and reports · 2022Review
- Advances in Cardiac Tissue Engineering.Bioengineering (Basel, Switzerland) · 2022Review
- Methods for vascularization and perfusion of tissue organoids.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- A novel soluble epoxide hydrolase vaccine protects murine cardiac muscle against myocardial infarction.Scientific reports · 2022Article
- Bioengineering Strategies to Create 3D Cardiac Constructs from Human Induced Pluripotent Stem Cells.Bioengineering (Basel, Switzerland) · 2022Review
- Review
- Cardiac organoid - a promising perspective of preclinical model.Stem cell research & therapy · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background2-Cl-C.OXT-A (COA-Cl) is a novel synthesized adenosine analog that activates Sphingosine-1-phosphate 1 receptor (S1P1R) and combines with the adenosine A1 receptor (A1R) in G proteins and was shown to enhance angiogenesis and improve the brain function in rat stroke models. However, the role of COA-Cl in hearts remains unclear. COA-Cl, which has a similar structure to xanthine derivatives, has the potential to suppress phosphodiesterase (PDE), which is an important factor involved in the beating of heart muscle. METHODS AND
resultsCardiac organoids with fibroblasts, human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs), and hiPSC-derived endothelial cells (hiPSC-ECs) were cultured until they started beating. The beating and contraction of organoids were observed before and after the application of COA-Cl. COA-Cl significantly increased the beating rate and fractional area change in organoids. To elucidate the mechanism underlying these effects of COA-Cl on cardiac myocytes, pure hiPSC-CM spheroids were evaluated in the presence/absence of Suramin (antagonist of A1R). The effects of COA-Cl, SEW2871 (direct stimulator of S1P1R), two positive inotropes (Isoproterenol [ISO] and Forskolin [FSK]), and negative inotrope (Propranolol [PRP]) on spheroids were assessed based on the beating rates and cAMP levels. COA-Cl stimulated the beating rates about 1.5-fold compared with ISO and FSK, while PRP suppressed the beating rate. However, no marked changes were observed with SEW2871. COA-Cl, ISO, and FSK increased the cAMP level. In contrast, the level of cAMP did not change with PRP or SEW2871 treatment. The results were the same in the presence of Suramin as absence. Furthermore, an enzyme analysis showed that COA-Cl suppressed the PDE activity by half.
conclusionsCOA-Cl, which has neovascularization effects, suppressed PDE and increased the contraction of cardiac organoids, independent of S1P1R and A1R. These findings suggest that COA-Cl may be useful as an inotropic agent for promoting angiogenesis in the future.
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