Cracking the Endothelial Calcium (Ca²⁺) Code: A Matter of Timing and Spacing

A monolayer of endothelial cells lines the innermost surface of all blood vessels, thereby coming into close contact with every region of the body and perceiving signals deriving from both the bloodstream and parenchymal tissues. An increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i) is the main mechanism whereby vascular endothelial cells integrate the information conveyed by local and circulating cues. Herein, we describe the dynamics and spatial distribution of endothelial Ca²⁺ signals to understand how an array of spatially restricted (at both the subcellular and cellular levels) Ca²⁺ signals is exploited by the vascular intima to fulfill this complex task. We then illustrate how local endothelial Ca²⁺ signals affect the most appropriate vascular function and are integrated to transmit this information to more distant sites to maintain cardiovascular homeostasis. Vasorelaxation and sprouting angiogenesis were selected as an example of functions that are finely tuned by the variable spatio-temporal profile endothelial Ca²⁺ signals. We further highlighted how distinct Ca²⁺ signatures regulate the different phases of vasculogenesis, i.e., proliferation and migration, in circulating endothelial precursors.