Dr. Ruhul Abid. The major focus of Dr. Abid's laboratory is to understand how reactive oxygen species (ROS) or redox-content of the endothelium modulates signal transduction and coronary vascular functions in vivo. It was Dr. Abid's pioneering work that showed that NADPH oxidase-derived reactive oxygen species (ROS) are essential for endothelial cell (EC) proliferation, migration and survival. Recently, his lab found that endothelium-dependent coronary arteriolar vasodilatation by VEGF requires NADPH oxidase-derived ROS to activate PI3K-Akt-eNOS and nitric oxide (NO) production (ATVB, 2010; PLoS ONE, 2011). The same study further demonstrated that lowering ROS levels resulted in decreased NO levels in intact coronary vessels suggesting that reduction in ROS disrupted activation of upstream c-Src and PI3K-Akt pathway. This study was awarded the best scientific work (Werner Risau New Investigator Award in Vascular Biology in 2011) among 650 original research work by the American Heart Association. The ongoing studies, in collaboration with Dr. Sellke's lab, using human coronary artery ECs and animal models are aimed at examining whether endothelium-specific conditional increase in ROS will have positive impact on coronary vasodilatation and collateral vessel growth in ischemic myocardium. To that end, Abid lab has generated binary conditional transgenic animal models that can temporally increase regulatable quantities of ROS specifically in the vascular endothelium. The outcome of these studies will have great impact on the development of novel therapeutic modalities for ischemic diseases, and may help explain the reasons for apparent failure of antioxidants in the major clinical trials.
“Improvement of Coronary Vascular Function by Endothelium-targeted Increase in ROS”
The goal of this study is to stimulate new blood vessel formation in diseased heart by short term, localized increase of reactive oxygen species (ROS) in the innermost layer of coronary blood vessels using a binary transgenic animal model.
14GRNT20460291Abid (PI) 07/01/14-06/30/17
“Mechanisms for Differential Effects of Short-term and Long-term Increase in ROS on Endothelium”
The goal of this study is to elucidate the mechanisms by which the duration of exposure to ROS modulate downstream signaling pathways and mitochondrial function in endothelium.