Ischaemic tissue released microvesicles induce monocyte reprogramming and increase tissue repair by a tissue...

Area of Science:

• Cardiovascular Biology
• Cell Biology
• Regenerative Medicine

Background:

• Monocytes can acquire endothelial features, but their role in angiogenesis post-ischaemia is unclear.
• Investigating monocyte participation in neovascularization after peripheral artery disease (PAD) is crucial for understanding tissue repair.

Purpose of the Study:

• To determine if ischaemic cells release microvesicles (MVs) that promote neovascularization in a PAD model.
• To elucidate the mechanism by which MVs influence monocyte differentiation and angiogenesis.

Main Methods:

• Hind-limb ischaemia (HLI) model in mice to study PAD.
• Isolation and phenotypic characterization of MVs from ischaemic muscle and blood.
• In vivo experiments using MVs from endothelial cells (ECs) overexpressing tissue factor (TF) or control MVs.

Main Results:

• HLI induced higher release of MVs containing tissue factor (TF) from muscle and blood.
• Endothelial cell-derived MVs (EMVs) induced monocyte (Mo) differentiation into endothelial cell-like (ECL) cells.
• Treatment with TF-rich EMVs significantly increased new vessel formation and Mo/macrophage integration in the ischaemic hind-limb.

Conclusions:

• Ischaemia-activated ECs release TF-rich EMVs that drive Mo differentiation into ECL cells.
• This process promotes new blood vessel formation in ischaemic zones.
• TF-mediated EMV release contributes to ischaemic tissue repair and neovascularization.