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Endothelial MerTK impairment accelerates the development of atherosclerosis

Shijie Liu1, Jingke Yao1, Hongye Huang1

  • 1Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.

Redox Biology
|September 15, 2025
PubMed
Abstract

Insights

Endothelial MER proto-oncogene tyrosine kinase (MerTK) deficiency promotes atherosclerosis by increasing inflammation and mitochondrial dysfunction. Impaired endothelial MerTK is a novel mechanism driving cardiovascular disease progression.

Area of Science:

  • Cardiovascular Biology
  • Inflammation Research
  • Molecular Mechanisms of Disease

Background:

  • Atherosclerosis is a major cause of cardiovascular disease, characterized by chronic arterial inflammation.
  • MER proto-oncogene tyrosine kinase (MerTK) is crucial for efferocytosis, the clearance of apoptotic cells.
  • The specific role of endothelial MerTK in atherosclerosis remains to be fully elucidated.

Purpose of the Study:

  • To investigate the contribution of endothelial MerTK to the development of atherosclerosis.
  • To elucidate the molecular mechanisms by which endothelial MerTK influences atherosclerosis progression.

Main Methods:

  • Utilized big data analytics, human microarray data, and proteomics.
  • Employed a unique mouse model with endothelial cell-specific MerTK deficiency (MerTKflox/floxTie2Cre).
  • Established an early-stage atherosclerosis model using a high-fat diet and AAV8-PCSK9 treatment.

Main Results:

  • Big data and human microarray analyses confirmed the predominant role of inflammation in atherosclerosis.
  • Endothelial MerTK deficiency in mice led to enhanced proinflammatory signaling, mitochondrial dysfunction, and MAPK pathway activation.
  • Endothelial dysfunction, smooth muscle cell alterations, and ultimately atherosclerosis development were promoted by MerTK deficiency.

Conclusions:

  • Endothelial MerTK deficiency significantly exacerbates atherosclerosis development.
  • Impairment of endothelial MerTK represents a novel mechanism promoting atherosclerosis.
  • The miR-218-5p/ECMerTK/MAPK axis is implicated in endothelial MerTK-mediated atherosclerosis.
Keywords:
AtherosclerosisBig data analyticsEndothelial cellsMerTKProteomics

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