The family of p90 ribosomal S6 kinases (RSKs) are pleiotropic effectors for extracellular signal-regulated kinase signaling pathways. Recently, RSK3 was shown to be important for pathological remodeling of the heart. Although cardiac myocyte hypertrophy can be compensatory for increased wall stress, in chronic heart diseases, this nonmitotic cell growth is usually associated with interstitial fibrosis, increased cell death, and decreased cardiac function. Although RSK3 is less abundant in the cardiac myocyte than other RSK family members, RSK3 appears to serve a unique role in cardiac myocyte stress responses. A potential mechanism conferring the unique function of RSK3 in the heart is anchoring by the scaffold protein muscle A-kinase anchoring protein β (mAKAPβ). Recent findings suggest that RSK3 should be considered as a therapeutic target for the prevention of heart failure, a clinical syndrome of major public health significance.
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http://dx.doi.org/10.1002/iub.1383 | DOI Listing |
J Cell Mol Med
December 2024
Institute of Cardiovascular Surgical Diseases, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Despite improvements in interventional techniques leading to faster myocardial reperfusion postmyocardial infarction, there has been a significant rise in the occurrence of myocardial ischaemia/reperfusion injury (MI/RI). A deeper understanding of the underlying mechanisms of MI/RI could offer a crucial approach to reducing myocardial damage and enhancing patient outcomes. This study examined the myocardial protective properties of puerarin (PUE) in the context of MI/RI using hypoxia/reoxygenation (H/R) or ischaemia/reperfusion (I/R) injury models were employed in H9c2 cells and C57BL/6 mice.
View Article and Find Full Text PDFNat 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 PDFCirculation
January 2025
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA (N.V., R.T.L.).
This editorial refers to “Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration” by Liu . and “YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division” by Morikawa
View Article and Find Full Text PDFSheng Wu Gong Cheng Xue Bao
December 2024
National Center for Protein Sciences (Beijing), Academy of Military Medical Sciences, Beijing 100850, China.
Retinoic acid signaling pathway plays a role in regulating vertebrate development, cell differentiation, and homeostasis. As a key enzyme that catalyzes the oxidation of retinal to retinoic acid, aldehyde dehydrogenase 1 family member A2 (Aldh1a2) is involved in cardiac development, while whether it functions in heart diseases remains to be studied. In this study, we infected primary cardiomyocytes with adenovirus overexpressing (Ad-Aldh1a2) to explore the effects of overexpression on the biological function of cardiomyocytes.
View Article and Find Full Text PDFJ Biomed Mater Res A
January 2025
Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, California, USA.
Conventional two-dimensional (2D) cardiomyocyte differentiation protocols create cells with limited maturity, which impairs their predictive capacity and has driven interest in three-dimensional (3D) engineered cardiac tissue models of varying maturity and scalability. Cardiac spheroids are attractive high-throughput models that have demonstrated improved functional and transcriptional maturity over conventional 2D differentiations. However, these 3D models still tend to have limited contractile and electrical maturity compared to highly engineered cardiac tissues; hence, we incorporated a library of conductive polymer microfibers in cardiac spheroids to determine if fiber properties could accelerate maturation.
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