NO/NOS system dysregulation as a key molecular mechanism in chemotherapy-induced cardiotoxicity: a review

Cardiotoxicity, as a side effect of chemotherapeutic treatments, represents a major limiting factor during anti-tumour therapies. This is usually evident by decreased cardiac function, and the cardiovascular diseases linked to chemotherapeutic agents can range from mild arrhythmias and hypertension to myocardial injuries and heart failure. One of the most important regulators of cardiovascular function is nitric oxide (NO), a small signalling molecule associated with multiple cardioprotective properties. The activity of NO producing enzymes, the nitric oxide synthases (NOSs), is tightly regulated by pathways responsible for maintaining the cardiovascular NO homeostasis. Thus, the dysregulation of the NO/NOS system could lead to severe pathologic changes in cardiomyocytes and endothelial cells. This narrative review examines the evidence on how chemotherapeutic agents affect cardiac NOS activity and NO signalling, and explores whether NO/NOS dysregulation may be considered as a relevant mechanism in the development of chemotherapy-induced cardiotoxicity.