Resistin-like molecule γ attacks cardiomyocyte membranes and promotes ventricular tachycardia
Year: 2025
Type: article
Abstract: Ventricular tachycardia disrupts the heart’s coordinated pump function, leading to sudden cardiac death. Neutrophils, which are recruited in high numbers to the ischemic myocardium, promote these arrhythmias. Comparing neutrophils with macrophages, we found that resistin-like molecule γ ( Retnlg or RELMγ) was the most differentially expressed gene in mouse infarcts. RELMγ is part of a pore-forming protein family that defends the host against bacteria by perforating their membranes. In mice with acute infarcts, leukocyte-specific Retnlg deletion reduced ventricular tachycardia. RELMγ elicited membrane defects that allowed cell exclusion dyes to enter the cardiomyocyte interior and also caused delayed afterdepolarizations and later cardiomyocyte death, both of which are strong arrhythmogenic triggers. Human resistin likewise attacked membranes of liposomes and mammalian cells. We describe how misdirected innate immune defense produces membrane leaks and ventricular arrhythmia.
Source: Science
Authors: Nina Kumowski, Steffen Pabel, Jana Grune, Noor Momin, Van K. Ninh, Laura Stengel, Kyle I. Mentkowski, Yoshiko Iwamoto, Yi Zheng, I-Hsiu Lee, Jessica Matthias, Jan O. Wirth, Fadi E. Pulous, Hana Seung, Alexandre Paccalet, Charlotte G. Muse, Kenneth K. Y. Ting, Paul Delgado, Andrew J. M. Lewis, Vaishali Kaushal, Antonia Kreso, Dennis Brown, Sikander Hayat, Rafael Kramann, Filip K. Swirski, Kamila Naxerova, Daniel C. Propheter, Lora V. Hooper, Michael A. Moskowitz, Kevin R. King, Nadia Rosenthal, Maarten Hulsmans, Matthias Nahrendorf
Institutions: Harvard University, Massachusetts General Hospital, Center for Systems Biology, University Hospital Regensburg, University of California San Diego, Kerckhoff Klinik, British Heart Foundation, University of Oxford, RWTH Aachen University, Erasmus MC, Icahn School of Medicine at Mount Sinai, The University of Texas Southwestern Medical Center, Howard Hughes Medical Institute, Jackson Laboratory, Imperial College London, University of Würzburg, Universitätsklinikum Würzburg
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G109265861, G1603729399, G170437431, Research Excellence (round 3), HD Upgrade to a Nikon A1R Confocal Imaging Platform, G8540302876, Biological Mechanisms of the Infarct Borderzone, Macrophage heterogeneity in atrial remodeling, Macrophages in Cardiovascular Health, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital
OpenAlex ID: W4414032964