Die Bedeutung von PCSK9 für die kardiale Monozyten-Infiltration, Zytokin-Synthese und extramedulläre Hämatopoese während des akuten Myokardinfarkts.
Ernährungswissenschaften
Zusammenfassung der Projektergebnisse
Sudden cardiac death, arising from pump failure during abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive phenotypic changes of heart leukocytes. Using a new model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, we discovered that resident and monocyte-derived macrophages protected against arrhythmia. Both, depleting recruited macrophages in Ccr2-/- mice or all macrophage subsets with Csf1 receptor inhibition increased ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36-/- and Mertk-/- mice, viewed together with deteriorated mitochondrial integrity and accelerated cardiomyocyte death in macrophages’ absence, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. In conclusion, myeloid cells profoundly influence ischemia-induced rhythm disorders.
Projektbezogene Publikationen (Auswahl)
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Erfindungsmeldung über ein neues Mausmodell mit ventrikulären Arrhythmien: spontaneous tachycardia occurred frequently in hypokalemic mice with MI (STORM)
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Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells. Nat Med; 25(11):1761-1771
Frodermann, Vanessa; Rohde, David; Courties, Gabriel; Severe, Nicolas; Schloss, Maximilian J.; Amatullah, Hajera; McAlpine, Cameron S.; Cremer, Sebastian; Hoyer, Friedrich F.; Ji, Fei; van Koeverden, Ian D.; Herisson, Fanny; Honold, Lisa; Masson, Gustavo Santos; Zhang, Shuang; Grune, Jana; Iwamoto, Yoshiko; Schmidt, Stephen P.; Wojtkiewicz, Gregory R.; ... & Nahrendorf, Matthias
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Multimodal imaging of bacterial-host interface in mice and piglets with Staphylococcus aureus endocarditis. Sci Transl Med.;12(568)
Panizzi, Peter; Krohn-Grimberghe, Marvin; Keliher, Edmund; Ye, Yu-Xiang; Grune, Jana; Frodermann, Vanessa; Sun, Yuan; Muse, Charlotte G.; Bushey, Kaitlyn; Iwamoto, Yoshiko; van Leent, Mandy M. T.; Meerwaldt, Anu; Toner, Yohana C.; Munitz, Jazz; Maier, Alexander; Soultanidis, Georgios; Calcagno, Claudia; Pérez-Medina, Carlos; Carlucci, Giuseppe; ... & Nahrendorf, Matthias
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Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease. Nature Cardiovascular Research volume 1, pages28–44
Rohde, David; Vandoorne, Katrien; Lee, I-Hsiu; Grune, Jana; Zhang, Shuang; McAlpine, Cameron S.; Schloss, Maximilian J.; Nayar, Ribhu; Courties, Gabriel; Frodermann, Vanessa; Wojtkiewicz, Gregory; Honold, Lisa; Chen, Qi; Schmidt, Stephen; Iwamoto, Yoshiko; Sun, Yuan; Cremer, Sebastian; Hoyer, Friedrich F.; Iborra-Egea, Oriol; ... & Nahrendorf, Matthias
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Electroimmunology and cardiac arrhythmia. Nat Rev Cardiol.;18(8):547-564
Grune, Jana; Yamazoe, Masahiro & Nahrendorf, Matthias
