Angiocrine endothelium: From physiology to atherosclerosis and cardiac repair

Cardiovascular diseases are the leading cause of mortality worldwide. In the presence of diabetes, mortality from cardiovascular disease is higher in women than in men. A better perception of the mechanisms common to atherosclerosis and diabetes, which lead to co-morbidities, is an exciting challenge. During embryogenesis, endothelial cells participate in organogenesis before development of the fetal circulation, suggesting that endothelial cells are capable of releasing paracrine trophogens, named angiocrine factors, promoting morphogenesis and repair of the adjacent parenchyma/stroma where the vessels lie. These exclusive specialized microvascular cells likely act through the release of angiocrine factors that possess specific cellular targets and play a pivotal role in atherosclerotic disease. A specific subset of microvascular endothelial cells displays highly sensitive feedbacks elicited by changes within the microenvironmental milieu and serves as powerful spatiotemporal sensor and effector to drive the secretion of specific angiocrine factors under normal and pathological conditions. An integration of basic and translational research may lead to the identification of endothelial cells dependent mechanisms that may fuel the increased prevalence of atherosclerotic disease and worse prognosis in diabetic patients. In this review, we will discuss the role of cardiovascular endothelial cells and their angiocrine factors in tissue homeostasis and disease, with a special focus on atherosclerotic disease and cardiac repair.