bims-hafaim 2026-05-10 papers

Issue of 2026–05–10
two papers selected by
Kyle McCommis, Saint Louis University

Proc Natl Acad Sci U S A. 2026 May 19. 123(20): e2602039123

Choice of cardioplegia influences metabolomics of human cardiac tissue.

Sho Tanosaki, Yuan Zhang, Kenneth Bedi, Kenneth Margulies, James E Cox, Zoltan Arany, E Dale Abel.

Cardioplegia is often used prior to acquisition of human cardiac tissue to minimize warm ischemia time, which can severely confound studies of cardiac metabolism. However, there are several choices of cardioplegia solutions, and whether these solutions differentially impact tissue metabolism or metabolomic studies is not known. Here, we perform untargeted metabolomics, using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry, on a large cohort of hearts transplanted for cardiomyopathy or from gift-of-life donors, and who have received different cardioplegia solutions. We show that different cardioplegia solutions distinctly impact cardiac metabolism and tissue metabolomic studies. Notably, these differences are mild relative to those seen comparing failing to nonfailing hearts, and identification of cardioplegia components in mass spectra should enable rigorous interpretation of changes between conditions. These data demonstrate how cardioplegia solutions may influence cardiac metabolism in human heart samples and underscore the need to report specific details of cardioplegia solution use in studies of human cardiac metabolism.

Keywords: cardioplegia; heart failure; metabolism; metabolomics

DOI: https://doi.org/10.1073/pnas.2602039123

J Mol Cell Cardiol Plus. 2026 Jun;16 100847

RMC-6272, a selective third-generation bi-steric mTORC1 inhibitor, improves cardiac function in pressure overload-induced cardiac hypertrophy.

Mariam Rogge, Johannes Fischer, Tobias Jakobi, Zoe Loewenthal, Parul Gupta, Lonny Jürgensen, Norbert Frey, Christoph Sandmann, Mirko Völkers.

Pathological remodeling in cardiomyocytes during heart failure is driven by excessive activation of mTORC1. Preclinical studies in mice demonstrated that reducing mTORC1 activity protects against cardiac dysfunction and hypertrophic remodeling. However, clinical application of current mTOR inhibitors is limited by incomplete mTORC1 inhibition and off-target effects, including suppression of mTORC2-mediated pro-survival signaling. To address these challenges, the therapeutic effects of the third-generation bi-steric mTORC1 inhibitor RMC-6272 was tested in pressure overload induced heart failure models. The potency and selectivity of RMC-6272 were evaluated in isolated cardiomyocytes. Hypertrophy was induced by phenylephrine in vitro and aortic banding in vivo. Cardiomyocyte-specific mRNA translation changes were assessed in αMHC-Cre Ribo-tag mice. RMC-6272 demonstrated superior potency and specificity for mTORC1 compared to rapamycin and Torin1. RMC-6272 prevented pathological hypertrophic growth in vitro and suppressed mTORC1-dependent mRNA translation, particularly those encoding components of the translational machinery. Preventive RMC-6272 treatment preserved cardiac function under pressure overload, maintaining contractile dysfunction in mice. Therapeutic treatment improved function in established hypertrophy, demonstrating therapeutic potential even after disease onset.

Keywords: Cardiac hypertrophy; Heart diseases; Heart failure; RMC-6272; mTOR; mTORC1

DOI: https://doi.org/10.1016/j.jmccpl.2026.100847