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Transcriptome Analysis Identified SPP1-Positive Monocytes as a Key in Extracellular Matrix Formation in Thrombi.

Takaya Kitano1,2, Tsutomu Sasaki2, Takahiro Matsui3,4

  • 1Department of Neurology Toyonaka Municipal Hospital Osaka Japan.

Journal of the American Heart Association
|September 30, 2025
PubMed
Summary
This summary is machine-generated.

Monocytes and macrophages expressing high levels of SPP1 are crucial for thrombus maturation. Targeting these cells may offer new strategies for treating thrombosis and preventing embolisms.

Keywords:
RNA sequencingextracellular matrixosteopontinstrokethrombosis

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Hematology

Background:

  • Thrombus stability influences natural course, persistence, and spontaneous dissolution.
  • Understanding thrombus maturation mechanisms is key for treating thrombosis and preventing embolisms.
  • Current knowledge on thrombus maturation processes remains incomplete.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying thrombus maturation.
  • To identify key genes and cellular players involved in thrombus stability.
  • To explore potential therapeutic targets for thrombosis.

Main Methods:

  • RNA sequencing of cerebral thrombi and matched blood samples.
  • Immunohistochemistry validation on 66 cerebral embolism thrombi.
  • Single-cell RNA sequencing of pulmonary artery thrombi.

Main Results:

  • 1121 genes were upregulated in thrombi, with extracellular matrix formation identified as a key pathway.
  • SPP1 (osteopontin) was identified as a hub gene, upregulated in thrombi.
  • SPP1-high monocytes/macrophages were identified, expressing extracellular matrix genes and correlating with thrombus resistance to thrombectomy.

Conclusions:

  • SPP1-high monocytes/macrophages play a critical role in thrombus maturation.
  • Osteopontin expression correlates with collagen type VI and thrombus resistance.
  • Targeting SPP1-expressing cells may be a novel therapeutic strategy for thrombosis.