Science Friday Talks

Get up-to-the-minute research discoveries on hot topics, such as Alzheimer’s disease, biological warfare and cancer.

Science Friday Talks

Get up-to-the-minute research discoveries on hot topics, such as Alzheimer’s disease, biological warfare and cancer.

The TGF-beta Pathway Mediates Vascular Damage by Doxorubicin

Dr. Eugene Konorev, Associate Professor, Division of Basic Sciences, Kansas City University of Medicine and Biosciences

Recent advances in anticancer therapy improved the prognosis and survival of cancer patients. Many anticancer drugs however exhibit serious cardiovascular complications. This talk focuses on doxorubicin, an anticancer anthracycline antibiotic that is known to cause cardiomyopathy in treated patients.

Doxorubicin cardiomyopathy responds poorly to therapy and often progresses to fatal congestive heart failure. Much of research efforts in the past emphasized cardiomyocyte as a primary target of doxorubicin in the heart. Our current study takes a fresh look at the cardiac action of doxorubicin in that it 1) considers endothelial cells as an important target of doxorubicin in the heart, and 2) recognizes the contribution of the TGF-beta pathway to the endothelial effects of doxorubicin.

Evidence is presented that deleterious effects of doxorubicin appear to be mediated by TGF-beta-Smad3 signaling as inhibition of the pathway using a small molecular weight inhibitor and a genetic Smad3 knockout alleviates its detrimental effects on endothelial cells.