Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions

Area of Science:

• Cell Biology
• Molecular Biology
• Vascular Biology

Background:

• Microvesicles (MVs) transfer cellular contents, modulating recipient cell function.
• Previous studies showed MVs from stimulated endothelial progenitor cells negatively impact endothelial cells.
• Endothelial microvesicles (EMVs) effects on human brain vascular smooth cells (HBVSMCs) remain largely unexplored.

Purpose of the Study:

• To investigate the impact of EMVs on HBVSMC proliferation, migration, and apoptosis.
• To elucidate the role of RNA cargo within EMVs in modulating HBVSMC function.
• To identify the molecular pathways involved in EMV-mediated effects on HBVSMCs.

Main Methods:

• EMVs were isolated from TNF-α plus serum deprivation (SD)-stimulated human brain microvascular endothelial cells (HBMECs).
• HBVSMCs were co-cultured with EMVs or RNase-treated EMVs to assess proliferation, migration, and apoptosis.
• Western blot and qRT-PCR were used to analyze key proteins (Mek1/2, Erk1/2, caspase-3, Bcl-2) and miR-146a-5p levels.

Main Results:

• EMVs significantly enhanced HBVSMC proliferation and migration, associated with increased Mek1/2 and p-Erk1/2.
• EMVs reduced HBVSMC apoptosis by ~35%, linked to decreased cleaved caspase-3 and increased Bcl-2.
• EMVs increased miR-146a-5p levels in HBVSMCs, and RNase treatment diminished these effects.

Conclusions:

• EMVs generated under inflammatory conditions modulate HBVSMC function and fate through their RNA cargo.
• The Mek1/2/Erk1/2 pathway and caspase-3/Bcl-2 regulation are implicated in these effects, with miR-146a-5p potentially playing a key role.
• These findings suggest EMVs from inflammation-challenged endothelial cells disrupt HBVSMC homeostasis, indicating potential therapeutic targets for vascular diseases.