The clinical use of doxorubicin in cancer is limited by cardiotoxic effects that can lead to heart failure. Whereas earlier work focused on the direct impact of doxorubicin on cardiomyocytes, recent studies have turned to the endothelium, because doxorubicin-damaged endothelial cells can trigger the development and progression of cardiomyopathy by decreasing the release and activity of key endothelial factors and inducing endothelial cell death. Thus, the endothelium represents a novel target for improving the detection, management, and prevention of doxorubicin-induced cardiomyopathy.
Keywords: AKT, protein kinase B; Bcl-2, B-cell lymphoma-2; DNA, deoxyribonucleic acid; ERK1/2, extracellular signal-regulated kinase 1/2; ET, endothelin; LV, left ventricular; MRP, multidrug resistance protein; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; NOS, nitric oxide synthase; NRG-1, neuregulin-1; PGI2, prostaglandin I2; PI3K, phosphoinositide 3-kinase; RNS, reactive nitrogen species; ROS, reactive oxygen species; ZO, zona occludens; cardiomyopathy; doxorubicin; endothelium; heart failure.