Contribution of pericyte paracrine regulation of the endothelium to angiogenesis.

During physiological development and after a stressor event, vascular cells communicate with each other to evoke new vessel formation-a process known as angiogenesis. This communication occurs via direct contact and via paracrine release of proteins and nucleic acids, both in a free form or encapsulated into micro-vesicles. In diseases with an altered angiogenic response, such as cancer and diabetic vascular complications, it becomes of paramount importance to tune the cell communication process. Endothelial cell growth and migration are essential processes for new vessel formation, and pericytes, together with some classes of circulating monocytes, are important endothelial regulators. The interaction between pericytes and the endothelium is facilitated by their anatomical apposition, which involves endothelial cells and pericytes sharing the same basement membrane. However, the role of pericytes is not fully understood. The characteristics and the function of tissue-specific pericytesis are the focus of this review. Factors involved in the cross-talk between these cell types and the opportunities afforded by micro-RNA and micro-vesicle techniques are discussed. Targeting these mechanisms in pathological conditions, in which the vessel response is altered, is considered in relation to identification of new therapies for restoring the blood flow.