Endothelial cells are of great importance in many types of diseases including the coronary artery diseases in heart and stroke in brain. In this review, we explore the heterogeneity among endothelial cells from an organism-wide, organ-specific, and healthy versus disease perspective.

Recent studies addressing the cellular heterogeneity between arterial versus venous endothelial cells (ECs) have revealed that arterial ECs have tighter junctions, a decreased immune response, anticoagulant properties while veins have both anticoagulant and procoagulant properties. Blood and lymphatic ECs are quite distinct from each other as well, with the lymphatic ECs being more involved in the immune response and lymphangiogenesis while blood vessel ECs being involved in angiogenesis and maintenance of perfusion throughout the body. ECs from various organs such as the heart, the lung, and especially the brain are quite heterogeneous and provide barriers that prevent small particles to pass through the endothelium when compared with the endothelium of the liver and the kidney that are quite porous. The heart ECs have higher angiogenesis and metabolic rates (oxidation and glycolysis) than lung, liver, and kidney ECs. Ex vivo liver and kidney ECs grow at a moderate pace, while the lung and brain ECs grow very slowly. ECs from within a tumor have fenestrae and large intracellular gaps and junctions leading to increased permeability and tumor cell overgrowth.

There is a large degree of heterogeneity among organism-wide and organ-specific ECs as well as between healthy and disease-specific ECs. We believe this review will help highlight the EC heterogeneity and further advance our ability to treat cardiovascular disease and other conditions.