Welcome to Cardiology Today – Recorded December 03, 2025. This episode summarizes 5 key cardiology studies on topics like H. O. P. E. and C. T. L. A. 4. Key takeaway: Osimertinib Heart Failure Via GATA4-MYLK3 Axis.
Article Links:
Article 1: Osimertinib induces reversible cardiac dysfunction through the GATA4-MYLK3-MYL2 axis. (European heart journal)
Article 2: Trained immunity in cardiovascular disease. (European heart journal)
Article 3: Safety and Tolerability of Sotagliflozin Among Kidney Transplant Recipients. (Transplantation)
Article 4: Anti-CTLA-4 Treatment Abrogates Co-stimulation Blockade-induced Acceptance of Transgenic Porcine Islets in Humanized Mice. (Transplantation)
Article 5: Cardiac Mitochondrial and Electrophysiological Changes in Transplanted Ovine Hearts Following Preservation by Hypothermic Oxygenated Perfusion. (Transplantation)
Full episode page: https://podcast.explainheart.com/podcast/osimertinib-heart-failure-via-gata4-mylk3-axis-12-03-25/
Featured Articles
Article 1: Osimertinib induces reversible cardiac dysfunction through the GATA4-MYLK3-MYL2 axis.
Journal: European heart journal
PubMed Link: https://pubmed.ncbi.nlm.nih.gov/41330421
Summary: This study found that osimertinib, a third-generation tyrosine kinase inhibitor, induces reversible cardiac dysfunction. The research demonstrated this cardiotoxicity operates through the GATA4-MYLK3-MYL2 axis. This mechanism explains the associated heart failure observed in patients treated with osimertinib for non-small cell lung carcinoma. Understanding this pathway provides a foundation for developing cardioprotective strategies against this drug-induced cardiac damage.
Article 2: Trained immunity in cardiovascular disease.
Journal: European heart journal
PubMed Link: https://pubmed.ncbi.nlm.nih.gov/41330410
Summary: Trained immunity, or T. R. I. M., is a recallable, long-term hyperinflammatory innate immune phenotype. This process involves changes in metabolic and epigenetic intracellular processes within mature innate immune cells. Trained immunity is identified as a core mechanism in the pathophysiology of atherosclerosis and represents a potential target for new pharmacological interventions to prevent or treat cardiovascular disease.
Article 3: Safety and Tolerability of Sotagliflozin Among Kidney Transplant Recipients.
Journal: Transplantation
PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40986618
Summary: Sodium-glucose cotransporter inhibitors effectively slow chronic kidney disease progression and reduce kidney failure events in the general population. These agents are known to cause an initial and sustained decline in estimated glomerular filtration rate and carry an increased risk of urogenital infections. For kidney transplant recipients, who face a high risk of adverse kidney outcomes, the safety and tolerability of this drug class, specifically sotagliflozin, are crucial considerations.
Article 4: Anti-CTLA-4 Treatment Abrogates Co-stimulation Blockade-induced Acceptance of Transgenic Porcine Islets in Humanized Mice.
Journal: Transplantation
PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40855395
Summary: Previous research demonstrated that beta cell-specific overexpression of a high-affinity variant of human cytotoxic T-lymphocyte-associated antigen 4, or C. T. L. A. 4, prevented porcine islet rejection in humanized mouse models. This study found that anti-cytotoxic T-lymphocyte-associated antigen 4 treatment abrogates the co-stimulation blockade, reversing the acceptance of transgenic porcine islets. This indicates that long-term xenograft function and survival were not maintained following neutralization of C. T. L. A. 4-mediated co-stimulation blockade.
Article 5: Cardiac Mitochondrial and Electrophysiological Changes in Transplanted Ovine Hearts Following Preservation by Hypothermic Oxygenated Perfusion.
Journal: Transplantation
PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40691830
Summary: Donor hearts experience injury during heart transplantation due to brain death and static cold storage preservation. Hypothermic oxygenated machine perfusion, or H. O. P. E., is a preservation method that may reduce myocardial injury compared to static cold storage. This study investigated specific cardiac mitochondrial and electrophysiological changes in transplanted ovine hearts following H. O. P. E. preservation. These findings are crucial for optimizing donor heart quality and improving heart transplant outcomes.
Transcript
Today’s date is December 03, 2025. Welcome to Cardiology Today. Here are the latest research findings.
Article number one. Osimertinib induces reversible cardiac dysfunction through the GATA4-MYLK3-MYL2 axis. This study found that osimertinib, a third-generation tyrosine kinase inhibitor, induces reversible cardiac dysfunction. The research demonstrated this cardiotoxicity operates through the GATA4-MYLK3-MYL2 axis. This mechanism explains the associated heart failure observed in patients treated with osimertinib for non-small cell lung carcinoma. Understanding this pathway provides a foundation for developing cardioprotective strategies against this drug-induced cardiac damage.
Article number two. Trained immunity in cardiovascular disease. Trained immunity, or T. R. I. M., is a recallable, long-term hyperinflammatory innate immune phenotype. This process involves changes in metabolic and epigenetic intracellular processes within mature innate immune cells. Trained immunity is identified as a core mechanism in the pathophysiology of atherosclerosis and represents a potential target for new pharmacological interventions to prevent or treat cardiovascular disease.
Article number three. Safety and Tolerability of Sotagliflozin Among Kidney Transplant Recipients. Sodium-glucose cotransporter inhibitors effectively slow chronic kidney disease progression and reduce kidney failure events in the general population. These agents are known to cause an initial and sustained decline in estimated glomerular filtration rate and carry an increased risk of urogenital infections. For kidney transplant recipients, who face a high risk of adverse kidney outcomes, the safety and tolerability of this drug class, specifically sotagliflozin, are crucial considerations.
Article number four. Anti-CTLA-4 Treatment Abrogates Co-stimulation Blockade-induced Acceptance of Transgenic Porcine Islets in Humanized Mice. Previous research demonstrated that beta cell-specific overexpression of a high-affinity variant of human cytotoxic T-lymphocyte-associated antigen 4, or C. T. L. A. 4, prevented porcine islet rejection in humanized mouse models. This study found that anti-cytotoxic T-lymphocyte-associated antigen 4 treatment abrogates the co-stimulation blockade, reversing the acceptance of transgenic porcine islets. This indicates that long-term xenograft function and survival were not maintained following neutralization of C. T. L. A. 4-mediated co-stimulation blockade.
Article number five. Cardiac Mitochondrial and Electrophysiological Changes in Transplanted Ovine Hearts Following Preservation by Hypothermic Oxygenated Perfusion. Donor hearts experience injury during heart transplantation due to brain death and static cold storage preservation. Hypothermic oxygenated machine perfusion, or H. O. P. E., is a preservation method that may reduce myocardial injury compared to static cold storage. This study investigated specific cardiac mitochondrial and electrophysiological changes in transplanted ovine hearts following H. O. P. E. preservation. These findings are crucial for optimizing donor heart quality and improving heart transplant outcomes.
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Keywords
H. O. P. E., C. T. L. A. 4, Xenotransplantation, heart failure, mitochondrial function, cardiovascular disease, cardiotoxicity, T. R. I. M., GATA4-MYLK3-MYL2 axis, innate immunity, Trained immunity, hypothermic oxygenated machine perfusion, islet rejection, kidney transplant recipients, non-small cell lung carcinoma, Osimertinib, Sotagliflozin, porcine islets, sodium-glucose cotransporter inhibitors, cytotoxic T-lymphocyte-associated antigen 4, cardiac preservation, Heart transplantation, S. G. L. T. i., atherosclerosis, chronic kidney disease.
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