Associate Professor of Biology & Principal Investigator of Molecular Toxicology Laboratory, Department of Biology, College of Arts and Science, the University of North Carolina at Greensboro.

Biograph
Dr. Zhenquan Jia earned his Ph.D in Biomedical & Veterinary Sciences from Virginia Polytechnic Institute and State University (Virginia Tech). Research in his laboratory is focused on investigating environmental chemical-induced vascular inflammation and injury with a special interest on understanding the possible signaling mechanisms involved. The environmental chemicals of interest include the anthracycline quinone (known as doxorubicin), polycyclic aromatic hydrocarbon (PAH)-derived- quinones and acrolein. In line with this research, funded by the NIH, we are also actively investigating the molecular mechanism(s) of action of novel bioactive compounds that target and reduce toxicant-mediated cardiovascular inflammation. The approaches include cell- and molecular biology techniques, and physiologically relevant animal models.

Speech Title: Soy isoflavone genistein attenuates vascular inflammation via targeting cAMP/PKA signaling

Abstract: Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1 μM-5 μM) significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis. Genistein also significantly suppressed TNF-α-induced production of adhesion molecules and chemokines such as sICAM-1, sVCAM-1, sE-Selectin, MCP-1 and IL-8, which play key role in the firm adhesion of monocytes to activated endothelial cells (ECs). Genistein at physiologically relevant concentrations didn't significantly induce antioxidant enzyme activities or scavenge free radicals. Further, blocking the estrogen receptors (ERs) in ECs didn't alter the preventive effect of genistein on endothelial inflammation. However, inhibition of protein kinase A (PKA) significantly attenuated the inhibitory effects of genistein on TNF-α-induced monocyte adhesion to ECs as well as the production of MCP-1 and IL-8. In animal study, dietary genistein significantly suppressed TNF-α-induced increase in circulating chemokines and adhesion molecules in C57BL/6 mice. Genistein treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, genistein protects against TNF-α-induced vascular endothelial inflammation both in vitro and in vivo models. This anti-inflammatory effect of genistein is independent of the ER-mediated signaling machinery or antioxidant activity, but mediated via the PKA signaling pathway.