Figure 3.

Overview of possible new therapeutics targeting the endothelium and thereby protecting the cardiomyocyte. Crosstalk between cardiomyocytes and endothelial cells is crucial for cardiac function. Endothelial cells constitute the inner lining of arteries, veins, and capillaries and form a barrier between vessels and heart. During cardiopulmonary bypass, the endothelium can be activated, leading to increased permeability of the endothelium (see top part of the schematic vessel), fluid accumulation, and tissue edema, thereby hampering oxygen exchange. Within the circulation, several proteins are up- or down-regulated during cardiopulmonary bypass. These circulating proteins can interfere with their receptors on the endothelium and also (in)directly affect the cardiomyocyte. They are, therefore, targets of interest to therapeutically protect the heart against IRI. VEGF-A = vascular endothelial growth factor A; VEGF-R2 = VEGF-receptor 2; S1PR1 = sphingosine-1-phosphate receptor 1; Tie2 = tyrosine kinase receptor; PAR1 = protease-activated receptor 1; WPB= Weibel–Palade bodies; Ca = calcium.