Researchers showed that mitochondrial pyruvate carrier (MPC) abundance mediates pathological cardiac hypertrophy. MPC abundance was reduced in failing hypertrophic human hearts, as well as in the myocardium of mice induced to fail by angiotensin II or through transverse aortic constriction.
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Fernandez-Caggiano, M., Kamynina, A., Francois, A. A., Prysyazhna, O., Eykyn, T. R., Krasemann, S., Crespo-Leiro, M. G., Vieites, M. G., Bianchi, K., Morales, V., Domenech, N., & Eaton, P. (2020). Mitochondrial pyruvate carrier abundance mediates pathological cardiac hypertrophy. Nature Metabolism, 1–9. https://doi.org/10.1038/s42255-020-00276-5 Cite
Researchers showed that hydrogen peroxide (H2O2), produced extracellularly, was necessary for the hypertrophic response of isolated cardiac myocytes and that aquaporin-1 facilitated the transmembrane transport of H2O2 through its water pore, resulting in activation of oxidant-sensitive kinases in cardiac myocytes.
[Science Translational Medicine]
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Montiel, V., Bella, R., Michel, L. Y. M., Esfahani, H., Mulder, D. D., Robinson, E. L., Deglasse, J.-P., Tiburcy, M., Chow, P. H., Jonas, J.-C., Gilon, P., Steinhorn, B., Michel, T., Beauloye, C., Bertrand, L., Farah, C., Zotti, F. D., Debaix, H., Bouzin, C., … Balligand, J.-L. (2020). Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide. Science Translational Medicine, 12(564). https://doi.org/10.1126/scitranslmed.aay2176 Cite
Scientists analyzed the applicability of a hydrojet-based method to deliver footprint-free iPSC-derived cardiomyocytes into the myocardium.
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Weber, M., Fech, A., Jäger, L., Steinle, H., Bühler, L., Perl, R. M., Martirosian, P., Mehling, R., Sonanini, D., Aicher, W. K., Nikolaou, K., Schlensak, C., Enderle, M. D., Wendel, H. P., Linzenbold, W., & Avci-Adali, M. (2020). Hydrojet-based delivery of footprint-free iPSC-derived cardiomyocytes into porcine myocardium. Scientific Reports, 10(1), 16787. https://doi.org/10.1038/s41598-020-73693-x Cite
Scientists investigated the immunomodulatory role of a liposomal azithromycin formulation in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects.
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Al-Darraji, A., Donahue, R. R., Tripathi, H., Peng, H., Levitan, B. M., Chelvarajan, L., Haydar, D., Gao, E., Henson, D., Gensel, J. C., Feola, D. J., Venditto, V. J., & Abdel-Latif, A. (2020). Liposomal delivery of azithromycin enhances its immunotherapeutic efficacy and reduces toxicity in myocardial infarction. Scientific Reports, 10(1), 16596. https://doi.org/10.1038/s41598-020-73593-0 Cite
The authors briefly survey cell sources and delivery strategies, along with biomaterials and their processing techniques, developed for myocardial infarction treatment. Key issues and challenges, as well as recommendations for future research, are also discussed.
[Advanced Healthcare Materials]
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Fibroblast-conditioned media (fCM)-mediated response seemed to be spatially-dependent as cardiomyocyte organoids treated with fCM had increased expression of connexin 40 and NAV1.5 primarily on its outer surface.
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Ribeiro da Silva, A., Neri, E. A., Turaça, L. T., Dariolli, R., Fonseca-Alaniz, M. H., Santos-Miranda, A., Roman-Campos, D., Venturini, G., & Krieger, J. E. (2020). NOTCH1 is critical for fibroblast-mediated induction of cardiomyocyte specialization into ventricular conduction system-like cells in vitro. Scientific Reports, 10(1), 16163. https://doi.org/10.1038/s41598-020-73159-0 Cite
Adult cardiac fibroblasts were freshly isolated and cultured on ECM topographical mimetics for 72 hours. Aligned mimetics caused cardiac fibroblasts to elongate while randomly organized topographies induced circular morphology similar to the disparate myofibroblast morphologies measured in vivo.
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Bugg Darrian, Bretherton Ross C, Kim Peter, Olszewski Emily, Nagle Abigail, Schumacher Austin E, Chu Nickolas, Gunaje Jagadambika, DeForest Cole A, Stevens Kelly, Kim Deok-Ho, & Davis Jennifer M. (n.d.). Infarct Collagen Topography Regulates Fibroblast Fate Via p38-Yap-TEAD Signals. Circulation Research, 0(0). https://doi.org/10.1161/CIRCRESAHA.119.316162 Cite
Researchers developed a matrigel-based hydrogel culture system to determine the roles of matrix stiffness and mechanotransduction in cardiac reprogramming. They found that soft matrix comparable with native myocardium promoted the efficiency and quality of cardiac reprogramming.
[Stem Cell Reports]
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Kurotsu, S., Sadahiro, T., Fujita, R., Tani, H., Yamakawa, H., Tamura, F., Isomi, M., Kojima, H., Yamada, Y., Abe, Y., Murakata, Y., Akiyama, T., Muraoka, N., Harada, I., Suzuki, T., Fukuda, K., & Ieda, M. (2020). Soft Matrix Promotes Cardiac Reprogramming via Inhibition of YAP/TAZ and Suppression of Fibroblast Signatures. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.07.022 Cite
54 patients were randomized to receive human umbilical cord-MSCs or bone-marrow-derived mononuclear cells in combination with coronary artery bypass-grafting (CABG) surgery. The control patients received no cells/vehicles but CABG intervention.
[International Journal of Stem Cells]
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Ulus, A. T., Mungan, C., Kurtoglu, M., Celikkan, F. T., Akyol, M., Sucu, M., Toru, M., Gul, S. S., Cinar, O., & Can, A. (n.d.). Intramyocardial Transplantation of Umbilical Cord Mesenchymal Stromal Cells in Chronic Ischemic Cardiomyopathy: A Controlled, Randomized Clinical Trial (HUC-HEART Trial). International Journal of Stem Cells. https://doi.org/10.15283/ijsc20075 Cite
The authors present a comprehensive overview of modified mRNA’s role in cardiomyocyte proliferation, cardiac vascularization, and prevention of cardiac apoptosis.
[Cardiovascular Drugs and Therapy]
Investigators employed single-cell transcriptomics combined with cell surface epitope detection by sequencing to investigate temporal neutrophil diversity in the blood and heart after murine myocardial infarction.