What is the clinical evidence from this study?

Study design: Other. Population: Acute myocardial infarction. Intervention: NK cell depletion (NK1.1 mAb) or genetic deletion vs. Isotype control or wild-type. Primary outcome: Infarct size and interstitial fibrosis (p=p=0.004 and p=0.036).

What question did this study set out to answer?

This research investigates the role of NK cells in heart injury and remodeling after myocardial infarction.

April 3, 2026Open Access

NK cells promote cardiac cell death and regulate myelopoiesis in myocardial infarction

Key Result

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.

Key Points

This research investigates the role of NK cells in heart injury and remodeling after myocardial infarction.
Assess recruitment and activation of NK cells in myocardial infarction using mouse models.
Evaluate the effects of NK cell genetic deletion and pharmacological depletion on cardiac function.
Analyze NK cell contributions to myelopoiesis and local GM-CSF production.
Activated NK cells cause cardiomyocyte apoptosis and adverse ventricular remodeling.
Depletion of NK cells leads to reduced cardiomyocyte death and improved cardiac function.
NK cell activation with anti-NKG2A antibody worsens ischemic heart failure symptoms.

Structured PICO

Does pharmacological depletion or genetic deletion of NK cells improve cardiac function and reduce adverse remodeling after acute myocardial infarction in mice?

Population

C57BL/6J mice subjected to permanent coronary artery ligation (MI model), genetically modified mice (Ccr2-/-, Nkp46iCre+/-R26RDTA, Ncr1gfp/gfp, Gzmb-/-, Nkp46Cre+/-Csf2lox/lox), and human ischemic heart tissue biopsies.

Intervention

Pharmacological depletion of NK cells (NK1.1 monoclonal antibody), genetic deletion of NK cells, or NK cell activation (anti-NKG2A monoclonal antibody).

Comparator

Isotype-treated control mice, sham-operated animals, or wild-type/littermate controls.

Outcome

Cardiac function (LV ejection fraction, cardiac output), infarct size, and interstitial fibrosis at day 21 post-MI.surrogate

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.

Main Result

p-value: p=0.004 and p=0.036

Abstract

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.

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