The role of PCSK9 on monocyte recruitment, cytokine synthesis and extramedullary hematopoiesis in acute myocardial infarction.
Nutritional Sciences
Final Report Abstract
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.
Publications
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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 V, Rohde D, Courties G, Severe N, Schloss MJ, Amatullah H, McAlpine CS, Cremer S, Hoyer FF, Ji F, van Koeverden ID, Herisson F, Honold L, Masson GS, Zhang S, Grune J, Iwamoto Y, Schmidt SP, Wojtkiewicz GR, Lee IH, Gustafsson K, Pasterkamp G, de Jager SCA, Sadreyev RI, MacFadyen J, Libby P, Ridker P, Scadden DT, Naxerova K, Jeffrey KL, Swirski FK, Nahrendorf M.
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Multimodal imaging of bacterial-host interface in mice and piglets with Staphylococcus aureus endocarditis. Sci Transl Med.;12(568)
Panizzi P, Krohn-Grimberghe M, Keliher E, Ye YX, Grune J, Frodermann V, Sun Y, Muse CG, Bushey K, Iwamoto Y, van Leent MMT, Meerwaldt A, Toner YC, Munitz J, Maier A, Soultanidis G, Calcagno C, Pérez-Medina C, Carlucci G, Riddell KP, Barney S, Horne G, Anderson B, Maddur-Appajaiah A, Verhamme IM, Bock PE, Wojtkiewicz GR, Courties G, Swirski FK, Church WR, Walz PH, Tillson DM, Mulder WJM, Nahrendorf M.
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Electroimmunology and cardiac arrhythmia. Nat Rev Cardiol.;18(8):547-564
Grune J, Yamazoe M, Nahrendorf M.
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Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease. Nature Cardiovascular Research volume 1, pages28–44
Rohde D, Vandoorne K, Lee I-H, Grune J, Zhang S, McAlpine CS, Schloss MJ, Nayar R, Courties G, Frodermann V, Wojtkiewicz G, Honold L, Chen Q, Schmidt S, Iwamoto Y, Sun Y, Cremer S, Hoyer FF, Iborra-Egea O, Muñoz-Guijosa C, Ji F, Zhou B, Adams RH, Wythe JD, Hidalgo J, Watanabe H, Jung Y, van der Laan AM, Piek JJ, Kfoury Y, Désogère PA, Vinegoni C, Dutta P, Sadreyev RI, Caravan P, Bayes-Genis A, Libby P, Scadden DT, Lin CP, Naxerova K, Swirski FK, Nahrendorf M.
