Fig. 1

Quiescent endothelial cells (ECs) participate to the physiological maintenance of cardiovascular tissue homeostasis through the control of vessel tone, permeability and intima thickness, coagulation and fibrinolysis, vessel remodelling and angiogenesis. Growth factors as VEGF, or peptides as BK and SP modulate the production/release of vasoactive molecules from ECs, including NO, PGI2, AngII and ET, which, in turn, activate intracellular signalling pathways as MAPK and cGMP pathways, and/or FGF2 production, involved in contractile function and EC survival and proliferation. Endothelial loss-of-function/dysfunction following exposure to conventional chemoterapeutic drugs or target therapies, including VEGF/VEGFR inhibitors. Cancer therapies damage essential signaling cascades that promote undesired cancer cell proliferation, but also protect endothelial cells, especially in response to stress. Endothelial dysfunction is regarded as a decrease of NO released from ECs, an increase of vessel permeability, an increase of platelet adhesion and aggregation, and transmigration of inflammatory cells, which in turn sustain atherosclerosis, vasoconstriction and reduced EC trofism and survival. Endothelial dysfunction is crucial in heart damage. Different categories of drugs have been shown to improve endothelial function and to reduce the risk of cardiovascular diseases associated to treatment with chemotherapeutic agents. Among these, there are ACEi, ARBs, renin and β1 antagonist, NO donor drugs, PKCε agonist and ALDH2 activators. (VEGF: vascular endothelial growth factor; BK: bradykinin; SP: substance P; NO: nitric oxide; ET: endothelin; PGI2: prostacyclin; AngII: angiotensin II; MAPK: Mitogen activated proteine kinase; cGMP: cyclic guanosine monophosphate; FGF2: fibroblast growth factor; VSMCs: vascular smooth muscle cells)