Ischemic tissue released microvesicles induce monocyte reprogramming and increase tissue repair by a tissue factor-dependent mechanism.

Neovascularization is the cornerstone of limb preservation in peripheral artery disease. Neovessel formation occurring during postnatal development is usually connected with inflammation. Advanced studies in the field of vascular biology have reported that monocytes can acquire endothelial features under angiogenic stimulation. We report that after ischemia affected endothelial cells release microvesicles rich in tissue factor that act as endogenous triggers by interacting with monocytes in an autocrine fashion, coaxing the cells to differentiate into functional endothelial cells. These differentiated cells have the ability to increase blood flow into ischemic tissue. The present study depicts a new concept in the mechanisms governing vessel formation in ischemic tissue.