Pharmacological depletion of natural killer cells significantly reduced infarct size (p=0.004) and interstitial fibrosis (p=0.036), and improved cardiac function after acute myocardial infarction.
Does pharmacological depletion or genetic deletion of NK cells improve cardiac function and reduce adverse remodeling after acute myocardial infarction in mice?
NK cells exacerbate post-ischemic heart failure by promoting cardiomyocyte apoptosis via Granzyme B and regulating bone marrow myelopoiesis, suggesting NK cell depletion as a potential therapeutic strategy.
p-value: p=0.004 and p=0.036
Abstract Ischemic heart failure remains a major clinical challenge, underscoring the need to better understand post-infarction immune mechanisms and identify new therapeutic targets. Both innate and adaptive immunity contribute to adverse cardiac remodeling following myocardial infarction (MI), yet the role of cytotoxic cells such as natural killer (NK) cells remains poorly defined. Here, we show that after acute MI in mice, NK cells are recruited to the ischemic myocardium in a CCR2-dependent manner and become activated. Activated NK cells locally release granzyme B, promoting cardiomyocyte apoptosis, adverse ventricular remodeling, and impaired cardiac function. Genetic deletion or pharmacological depletion of NK cells reduces cardiomyocyte death, attenuates inflammation, limits myocardial injury, and improves cardiac function. In contrast, NK cell activation using an anti-NKG2A monoclonal antibody exacerbates ischemic heart failure. We further demonstrate that NK cells regulate bone marrow myelopoiesis through local GM-CSF production. Finally, we identify a distinct NK cellular and transcriptomic signature in human ischemic heart tissue at early stages. Together, these findings reveal a detrimental role for NK cells following acute MI and highlight NK cells as potential therapeutic targets to limit adverse cardiac remodeling.
Cohen et al. (Wed,) conducted a other in Acute myocardial infarction. NK cell depletion (NK1.1 mAb) or genetic deletion vs. Isotype control or wild-type was evaluated on Infarct size and interstitial fibrosis (p=p=0.004 and p=0.036). Pharmacological depletion of natural killer cells significantly reduced infarct size (p=0.004) and interstitial fibrosis (p=0.036), and improved cardiac function after acute myocardial infarction.