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Crosstalk of human coronary perivascular adipose-derived stem cells with vascular cells: role of tissue factor

  • 0Cardiovascular-Program, Institut de Recerca Sant Pau, IIB-Sant Pau, Carrer Sant Quintí, 77-79, 08041, Barcelona, Spain. garderiu@santpau.cat.
Basic Research in Cardiology +

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March 2, 2024

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March 2, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Coronary perivascular adipose tissue stem cells (ASCs) regulate vascular smooth muscle cells (VSMCs) via tissue factor (TF) expression, impacting angiogenesis and cardiac protection. This discovery offers a new therapeutic target for cardiovascular disease.

Area Of Science

  • Cardiovascular Biology
  • Stem Cell Research
  • Adipose Tissue Biology

Background

  • Coronary perivascular adipose tissue (cPVAT) is linked to cardiovascular risk factors and atherosclerosis.
  • The role of resident mesenchymal stem cells (ASCs) within cPVAT in regulating vascular smooth muscle cells (VSMCs) remains unclear.
  • Existing hypotheses focus on adipokines, not cellular interactions within cPVAT.

Purpose Of The Study

  • To investigate the interactions between resident PVAT-ASCs and VSMCs.
  • To determine if PVAT-ASCs influence VSMC behavior and angiogenesis.
  • To explore potential differences in PVAT-ASC function based on cardiac disease etiology.

Main Methods

  • ASCs were isolated from human coronary PVAT of heart transplant recipients (ischemic vs. non-ischemic disease).
  • Phenotypic characterization, proliferation, and differentiation assays were performed on ASCs.
  • Co-culture studies examined crosstalk between ASCs and VSMCs, including ERK1/2-ETS1 signaling and tissue factor (TF) expression.
  • In vivo studies assessed angiogenic potential using implanted plugs in mice.

Main Results

  • PVAT-ASCs were identified in the adventitia with differentiation and angiogenic potential.
  • ASCs from ischemic PVAT exhibited distinct TF expression and VSMC recruitment compared to non-ischemic PVAT-ASCs.
  • TF upregulation in ischemic ASCs restored angiogenic capacity; TF silencing in non-ischemic ASCs reduced it.
  • A novel mechanism involving TF-mediated regulation of VSMCs by PVAT-ASCs in angiogenesis was identified.

Conclusions

  • PVAT-ASCs play a novel regulatory role in VSMC behavior and angiogenesis.
  • Tissue factor expression in PVAT-ASCs is a key mediator of this regulation.
  • Targeting TF in PVAT-ASCs presents a potential therapeutic strategy for enhancing cardiac protection.

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