Gene Therapy Alleviates Doxorubicin-Induced Cardiotoxicity

Gene Therapy Alleviates Doxorubicin-Induced Cardiotoxicity
Gene Therapy Alleviates Doxorubicin-Induced Cardiotoxicity

Vascular endothelial growth factor-B (VEGF-B) therapy may reduce the cardiotoxic effects of doxorubicin, according to study findings published in the Proceedings of the National Academy of Sciences (PNAS).1,2

Although doxorubicin is commonly used to treat many cancers, its use is limited due to cumulative cardiac atrophy and body wasting in patients receiving the drug. However, treatments to reverse these effects are limited. Because VEGF-B promotes coronary arteriogenesis, physiological cardiac hypertrophy, and ischemia resistance, the researchers hypothesized that VEGF-B may prevent doxorubicin-induced blood vessel rarefaction.

For the study, the researchers administered an adeno-associated viral vector expressing VEGF-B or a control vector to normal and tumor-bearing mice 1 week before treatment with doxorubicin. Doses given to the mice were comparable to the concentrations used in human treatment.

The researchers found that the gene therapy completely inhibited doxorubicin-induced cardiac atrophy and whole-body wasting, prevented capillary rarefaction in the heart, and improved endothelial function in the doxorubicin-treated mice.

In addition, the researchers noted left ventricular volume was increased without compromising cardiac function, expression of the gene associated with pathologic remodeling was reduced, and cardiac mitochondrial respiration was improved.

Furthermore, the gene therapy did not have an effect on doxorubicin concentrations in serum or tissue, nor did it augment tumor growth.

“By inhibiting doxorubicin-induced endothelial damage, VEGF-B could provide a novel therapeutic possibility for the prevention of chemotherapy-associated cardiotoxicity in cancer patients,” concluded the authors.

Reference

1. Räsänen M, Degerman J, Nissinen TA, et al. VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection. Proc Natl Acad Sci U S A. 2016 Oct 31. doi: 10.1073/pnas.1616168113. [Epub ahead of print]

2. A common heart problem caused by cancer therapy avoided blood vessel treatment [news release]. EurekAlert! web site. https://www.eurekalert.org/pub_releases/2016-10/uoh-ach103116.php. Accessed November 3, 2016.

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