Targeted anti-IL-1β platelet microparticles for cardiac detoxing and repair

Sci Adv. 2020 Feb 5;6(6):eaay0589. doi: 10.1126/sciadv.aay0589. eCollection 2020 Feb.

Abstract

An acute myocardial infarction (AMI) induces a sterile inflammatory response that facilitates further heart injury and promotes adverse cardiac remodeling. Interleukin-1β (IL-1β) plays a central role in the sterile inflammatory response that results from AMI. Thus, IL-1β blockage is a promising strategy for treatment of AMI. However, conventional IL-1β blockers lack targeting specificity. This increases the risk of serious side effects. To address this problem herein, we fabricated platelet microparticles (PMs) armed with anti-IL-1β antibodies to neutralize IL-1β after AMI and to prevent adverse cardiac remodeling. Our results indicate that the infarct-targeting PMs could bind to the injured heart, increasing the number of anti-IL-1β antibodies therein. The anti-IL-1β platelet PMs (IL1-PMs) protect the cardiomyocytes from apoptosis by neutralizing IL-1β and decreasing IL-1β-driven caspase-3 activity. Our findings indicate that IL1-PM is a promising cardiac detoxification agent that removes cytotoxic IL-1β during AMI and induces therapeutic cardiac repair.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blood Platelets / metabolism*
  • Cell-Derived Microparticles / metabolism*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / antagonists & inhibitors*
  • Mice
  • Models, Biological
  • Myocardial Infarction / etiology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / metabolism
  • Protein Binding
  • Ventricular Remodeling

Substances

  • Cytokines
  • IL1B protein, human
  • Inflammation Mediators
  • Interleukin-1beta