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 efficiently respond with 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 altered angiogenic response, such as that in tumors and during diabetic vascular complications, it becomes of paramount importance to tune above cell communication process. Endothelial cell growth and migration are essential processes for the new vessel formation, and pericytes, together with some classes of circulating monocytes, are potent endothelial regulators. The interaction between pericytes and the endothelium is facilitated by their anatomical reciprocal position in the vessels, whereby endothelial cells and pericytes share same basement membrane. In spite of their central role in controlling the vascular tree, the identity and function of pericytes are still not completely known. The presence and the bio-function of tissue-specific pericytes, in addition to the known mechanisms of the paracrine interaction with endothelial cells, will be the focus of this review. Typical factors involved in the cross-talk between above cell types and the potential new features represented by micro-RNAs and micro-vesicles will be discussed. Targeting these mechanisms in pathological conditions, in which the vessel response is altered, is the basis of new therapies that could be effective in restoring the blood flow.