Anti-cancer therapy induces endothelial dysfunction in the human microcirculation that is prevented by VEGF-B overexpression

The present study is the first to demonstrate longitudinal declines in microvascular endothelial function in breast cancer patients undergoing anti-cancer therapy. Microvascular dysfunction persists for several months after treatment, which may have implications for elevated cardiovascular risk in cancer patients. Therapies with a high risk of cardiotoxicity (doxorubicin and trastuzumab) induce vasomotor impairments in healthy arterioles ex vivo. These findings highlight microvascular endothelial dysfunction as a consequence of anti-cancer therapy which may contribute to treatment-induced cardiotoxicity. The microcirculation represents a potential therapeutic target for intervention to prevent or predict adverse cardiovascular outcomes in breast cancer patients. Overall design: Endothelial cells were grown from adipose tissue collected from donors without known cardiovascular disease. Endothelial cells isolated from surgical discard tissue (sample table below) were cultured and used for gene expression profiling of the effects of 0.1µM doxorubicin (DOX), 10µg/ul trastuzumab (TZM), 1µM paclitaxel (PTX) and their respective controls (media only for DOX and TZM; DMSO for PTX).