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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Mechanisms of failed apoptotic cell clearance by phagocyte subsets in cardiovascular disease

Edward B Thorp1

  • 1Department of Medicine, Columbia University, New York, NY 10032, USA. ebt2103@columbia.edu

Apoptosis : an International Journal on Programmed Cell Death
|June 17, 2010
PubMed

Insights

Defective clearance of dying cells, known as efferocytosis, drives atherosclerosis progression. Targeting efferocytosis defects could resolve inflammation and prevent heart disease.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Cellular Biology

Background:

  • Defective efferocytosis (phagocytic clearance of apoptotic cells) contributes to advanced atherosclerotic lesions, a precursor to atherothrombosis and ischemic heart disease.
  • During atherogenesis, efficient efferocytosis maintains lesion integrity, but defects lead to secondary necrosis and plaque instability.
  • Key molecular regulators like MERTK, MFGE8, and C1q are implicated in efferocytosis defects during atherosclerotic progression.

Purpose of the Study:

  • To outline a model where plaque necrosis is promoted by inhibited efferocytosis signaling and expanded populations of inefficient phagocytes.
  • To identify potential in vivo suppressors of efferocytosis in atherosclerosis.
  • To explore interventional targets for enhancing efferocytosis and resolving inflammation in cardiovascular disease.

Main Methods:

  • Review of recent evidence in humans and genetic causation studies in experimental rodents.
  • Analysis of cellular mechanisms and molecular regulators of efferocytosis in vascular wall phagocytes.
  • Discussion of potential in vivo suppressors and their differential effects on vascular phagocyte subsets.

Main Results:

  • Atheromata contain diverse phagocyte populations (monocytes, macrophages, dendritic cells) with varying efferocytosis efficiencies.
  • Plaque necrosis and destabilization result from inhibited phagocytic signaling pathways and the expansion of phagocyte subsets with poor clearance capacity.
  • MER tyrosine kinase (MERTK), milk fat globule-EGF factor 8 (MFGE8), and complement C1q are key molecular regulators implicated in efferocytosis defects.

Conclusions:

  • Defective efferocytosis is a critical factor in atherosclerotic lesion progression and plaque instability.
  • Targeting efferocytosis pathways and optimizing phagocyte function presents a promising therapeutic strategy for atherosclerosis and ischemic heart disease.
  • Understanding the differential impact of interventions on vascular phagocyte subsets is crucial for developing effective treatments.

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