The effects of β adrenergic receptors (β-ARs) and p38 mitogen-activated protein kinases (MAPK) pathways on cardiosphere-derived cells (CDCs) are largely unknown. This study aimed to investigate the roles of β-ARs and p38MAPK pathways on the proliferation, apoptosis, and differentiation capacity of CDCs. The CDCs were treated with β1-AR blocker (Met group), β2-AR antagonist (ICI group), and p38MAPK inhibitor (SB group), non-selective β-AR blocker (PRO group), and β-AR agonist (ISO group). The viability, apoptotic rate and differentiation status of CDCs were determined by MST-1 assay, flow cytometery, and Western blot, respectively. The CDCs viability significantly reduced in ICI group (all P < 0.05), and SB group had a significant high viability after 48 h treatment (P < 0.05). Compared with control group, all treated groups had a low apoptotic rate. After treatment for 72 h, ISO treatment elevated the expression of Nkx2.5, and could partially or fully attenuate the inhibitory effects of β-AR antagonists and/or p38MAPK inhibitor. A similar overall trend of protein expression levels among all groups could be observed between protein pairs of cTnT and β1-AR as well as c-Kit and β2-AR, respectively. These results suggested that β-ARs and p38MAPK signaling pathways play crucial roles in the proliferation and differentiation of CDCs. Our findings should be helpful for better understanding the molecular mechanism underlying the physiological processes of CDCs.
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http://dx.doi.org/10.1002/jcb.26292 | DOI Listing |
Front Cardiovasc Med
December 2024
Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Despite improvements in clinical outcomes of acute myocardial infarction (AMI), mortality rates remain high, indicating the need for further understanding of the pathogenesis and developing more effective cardiac protection strategies. Extracellular vesicles (EVs) carry proteins and noncoding RNAs (ncRNAs) derived from different cardiac cell populations, mainly including cardiomyocytes, endothelial cells, endothelial progenitor cells, cardiac progenitor cells, cardiosphere-derived cells, immune cells, fibroblasts and cardiac telocytes have vital roles under both physiological and pathological process such as myocardial infarction (MI). The content of EVs can also indicate the status of their parental cells and serve as a biomarker for monitoring the risk of cardiac injury.
View Article and Find Full Text PDFJ Am Heart Assoc
November 2024
Department of Regenerative Medicine, Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan.
Circ Res
September 2024
Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
All Food and Drug Administration-approved noncoding RNA (ncRNA) drugs (n≈20) target known disease-causing molecular pathways by mechanisms such as antisense. In a fortuitous evolution of work on regenerative medicine, my coworkers and I inverted the RNA drug discovery process: first we identified natural disease-modifying ncRNAs, then used them as templates for new synthetic RNA drugs. Mechanism was probed only after bioactivity had been demonstrated.
View Article and Find Full Text PDFFASEB J
September 2024
Department of Medicine, Division of Cardiology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
The objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere-derived cell (CDC) extracellular vesicles (EVs) delivered via intramyocardial and intravenous routes following acute myocardial infarction (MI). Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following MI. While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution and requirement for intramyocardial delivery.
View Article and Find Full Text PDFFront Pharmacol
August 2024
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
The heart is a multicellular system, and the intercellular crosstalk mechanism is very important for the growth and development of the heart and even the organs, tissues, and cells at a distance. As a kind of extracellular vesicle, exosomes are released by different types of cells and can carry specific genetic material, endosomal proteins, cytokines, etc., which are the main material basis for mediating cell crosstalk mechanism.
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