PI3K isoforms in vascular biology, a focus on the vascular system-Immune response connection

Cardiovascular diseases are the most common cause of death around the world. Hypertension and atherosclerosis, along with their sequalae and consequent target organ damage, constitute the main vascular risk factors contributing to theonset of cardiovascular disease. Disturbances in the homeostatic relationship established among the various components of the vascular milieu-namely endothelial and smooth muscle cells, adventitia, immune cells, and fibers of the autonomic nervous system-trigger the development of these arterial pathologies. In terms of molecular targets involved in vascular dysfunction and appealing for therapeutic purposes, the multitude of functions that phosphoinositide-3-kinases (PI3K) perform has become an attractive area of investigation in the field of arterial diseases. Composed of eight members arranged in III different classes based on their structure and substrate specificity, PI3Ks are characterized by their shared capability to produce phosphoinositides but, at the same time, they provide specificity and non-redundancy, owing to differences in expression levels of each member in different cell components of the vascular environment, different activation mechanisms and specific subcellular locations. This chapter aims at providing an overview of the functions of the different PI3K isoforms identified thus far in the vasculature, focusing on the emerging relationship established by components of the vascular and immune systems, at the steady-state and during pathology.