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TGFβ1 Regulates Cellular Composition of In Vitro Cardiac Perivascular Niche Based on Cardiospheres

Yu D Goltseva1, K V Dergilev2, M A Boldyreva2

  • 1National Medical Research Centre of Cardiology named after academician E. I. Chazov, Moscow, Russia. eleagnusom@gmail.com.

Bulletin of Experimental Biology and Medicine
|July 4, 2024
PubMed

Insights

Transforming growth factor beta 1 (TGFβ1) impacts cardiac perivascular niche cells. TGFβ1 stabilizes vascular cells, decreasing microvasculature length and endothelial cell proliferation while promoting mural cell differentiation.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Biology
  • Tissue Engineering

Background:

  • The cardiac perivascular niche, a critical microenvironment surrounding blood vessels, plays a vital role in cardiac health.
  • Understanding the regulatory principles governing this niche is essential for developing effective cardiac regenerative therapies.
  • The specific effects of growth factors like transforming growth factor beta 1 (TGFβ1) on niche cell behavior remain incompletely elucidated.

Purpose of the Study:

  • To investigate the impact of TGFβ1 on the cellular components of the cardiac perivascular niche.
  • To analyze the functional and phenotypic changes in progenitor, endothelial, and mural cells within the niche upon TGFβ1 stimulation.
  • To explore the potential role of TGFβ1 in vascular stabilization and cell differentiation within the cardiac microenvironment.

Main Methods:

  • Utilized a 3D cell culture model, cardiospheres, to mimic the cardiac perivascular niche.
  • Characterized cardiospheres for progenitor (c-Kit), endothelial (CD31), and mural (αSMA) cells, alongside basement membrane (laminin) and extracellular matrix proteins (collagen I, fibronectin).
  • Quantified the effects of TGFβ1 treatment on microvasculature length, specific cell populations (NG2+, αSMA+), and protein expression levels (VE-cadherin, transgelin/SM22α).

Main Results:

  • TGFβ1 treatment led to a significant decrease in the length of CD31+ microvasculature and VE-cadherin protein levels, indicating reduced endothelial integrity.
  • A reduction in NG2+ cells and an increase in αSMA+ cells and transgelin/SM22α protein levels were observed, suggesting a shift towards mural cell differentiation.
  • These findings suggest TGFβ1 may exert a stabilizing effect on vascular cells by inhibiting endothelial proliferation and promoting mural cell activation.

Conclusions:

  • TGFβ1 modulates the cardiac perivascular niche by influencing endothelial and mural cell populations.
  • The observed effects suggest TGFβ1 plays a role in vascular stabilization and differentiation within the cardiac niche.
  • Further research into TGFβ1's mechanisms could inform therapeutic strategies for cardiovascular diseases.

Keywords:
TGFβ1cardiospherescell microenvironmentendotheliumperivascular niche

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