Abstract A24: Endothelial cell aging and possible role in angioprevention: increased expression of TGFβ and other antiangiogenic factors

A24

Alterations of endothelium are associated with increased risk in cardiovascular diseases; they are also involved in tumor angiogenesis, one of the main “rate limiting step” in tumor progression and spreading. For this reason in the last years several agents have been patented for the cancer therapy thanks to their ability to inhibit tumor angiogenesis and now angiogenesis is considered also a target prevention.

Since senescence is considered an “anti-cancer” phenomenon we are evaluating the molecular changes that occur during aging in endothelial cells. We conducted this study on endothelial cells derived from Human Umbilical Vein (HUVECs) of ealry and late passages, fromboth masculin and feminin origin and we have analyzed the expression profile at different stages of in culture aging.

Several genes are regulated during this process; among these there is a significant reduction of the expression of genes such as E-selectin and CCL2 from cells of both male or female origin. This reduction could correlate with a decrease of the ability of endothelial cells to recruit inflammatory cells, and may have implications for metastatic spread of cancer. Angiopoietin 2 (ANG2) also seem to decrease during the endothelial cell senescence; this could be related to a potential impairment of the capacity to undergo remodeling in “aged” vessels. Interestingly, all three genes show a 2-fold higher expression in females as compared to males and the rate of decrease is different although the trend is the same. These data could suggest that there may be important gender-specific differences in gene expression of endothelial cells, and that these may have an effect on the senescence process.

Finally we have evidence that TGFβI, a molecule related to TGFβinduction, is increased with passages in culture and is very high in aged endothelial cells. Probably it could clarify the pro-apoptotic and antiangiogenic activity of TGFβ.

Taken together, these data confirm that physiological endothelial cell senescence could be associated with a reduction in anti-angiogenic potential; this property suggests that some tumors could be less angiogenic in the elderly.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A24.