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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
Summary
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.
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