Regulation of Notch Signaling Pathway to Innate Lymphoid Cells in Patients with Acute Myocardial Infarction

Area of Science:

• Immunology
• Cardiovascular Disease Research
• Cell Signaling

Background:

• The Notch signaling pathway regulates innate lymphoid cell (ILC) fate and immune responses.
• Its specific role in ILCs within acute coronary syndrome (ACS) remains unclear.

Purpose of the Study:

• To investigate the function of Notch signaling in ILCs during acute coronary syndrome.
• To determine the impact of Notch signaling on ILC subsets in unstable angina pectoris (UAP) and acute myocardial infarction (AMI) patients.

Main Methods:

• Analyzed mRNA expression of Notch receptors/ligands in peripheral blood mononuclear cells (PBMCs) and lin- cells from UAP, AMI patients, and controls using real-time PCR.
• Quantified ILC subsets via flow cytometry.
• Assessed ILC subsets, transcription factors, and cytokines after inhibiting Notch signaling with a gamma-secretase inhibitor (GSI) in lin- cells from AMI patients.

Main Results:

• Elevated Notch receptor and ligand mRNA levels were observed in PBMCs and lin- cells of AMI patients.
• While total ILC frequency remained unchanged, ILC1 subsets were down-regulated and ILC2 subsets were up-regulated in AMI patients.
• Notch inhibition via GSI increased ILC1 frequency and interferon-gamma secretion while decreasing ILC2 frequency and interleukin-5/13 production in AMI patient-derived cells.

Conclusions:

• Activated Notch signaling may drive an ILC1-to-ILC2 shift in the peripheral blood of AMI patients.
• Targeting Notch signaling could be a therapeutic strategy for modulating ILC responses in ACS.