Research findings, “Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells,” are discussed in a new report. “Inhibition of endothelial cell proliferation and angiogenesis is emerging as an important strategy in cancer therapeutics. Kringle 5 (K5) of human plasminogen is a potent angiogenesis inhibitor,” investigators in the United States report.
“Previous studies have shown K5 exposure promotes caspase activity and apoptosis in endothelial cells. Here we report that K5 treatment evokes an autophagic response in endothelial cells that is specific and initiated even in the absence of nutritional stress. Endothelial cells exposed to K5 up-regulated Beclin 1 levels within a few hours. Furthermore, progressively increasing amounts of antiapoptotic Bcl-2 were found to be complexed with Beclin 1, although total levels of Bcl-2 remained unchanged. Prolonged exposure to K5 ultimately led to apoptosis via mitochondrial membrane depolarization and caspase activation in endothelial cells. Knocking down Beclin 1 levels by RNA interference decreased K5 induced autophagy but accelerated K5-induced apoptosis,” wrote T.M. Nguyen and colleagues, University of Minnesota, Department of Pharmacology.

The researchers concluded: “These studies suggest that interfering with the autophagic survival response can potentiate the antiangiogenic effects of Kringle 5 in endothelial cells.”

Nguyen and colleagues published their study in Blood (Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells. Blood, 2007;109(11):4793-802).

For additional information, contact T.M. Nguyen, University of Minnesota Medical School, Dept. of Pharmacology, 321 Church Street SE, Minnesota, MN 55455 USA.

The publisher of the journal Blood can be contacted at: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA