Endothelial heterogeneity and their relevance in cardiac development and coronary artery disease

Micro- and macrovascular endothelial cells (ECs) are characterized by structural and functional heterogeneity, which is also reflected in their secretory activity. The root of this heterogeneity and related regulatory mechanisms are still poorly understood. During embryogenesis, microvascular ECs participate in organogenesis prior to the development of the fetal circulation, suggesting that ECs are capable of releasing paracrine trophogens, termed angiocrine factors (AFs). These are angiocrine growth factors, adhesion molecules, and chemokines, which are intended to promote morphogenesis and repair of the adjacent parenchyma/stroma where the vessels are located. There is a tissue and organ-specificity of AFs that traces the heterogeneity of ECs. This AF heterogeneity also traces how ECs respond to pathological conditions or exposure to cardiovascular risk factors. The study of the mechanisms that regulate endothelial and paracrine heterogeneity and that contribute to endotheliopathy represents a broad and as yet understudied area of research. A better understanding of the cellular and molecular mechanisms that regulate this heterogeneity, leading to endotheliopathy is an exciting challenge. In this brief review we will discuss experimental advances in the heterogeneity of ECs and their AF, with a focus on their involvement in the pathogenesis of coronary artery disease.