Date(s) - 11/12/2021
3:05 pm - 4:05 pm
Endothelial Mechanobiology: May the Flow Be With You
B. Rita Alevriadou, Ph.D.
Empire Innovation Professor in Biomedical Engineering, University at Buffalo – SUNY
Date: Friday, November 12, 2021
Time: 3:05 p.m.
Location: SCOB 228
Endothelial cell (EC) dysfunction is the hallmark of cardiovascular diseases and most of them are associ-ated with altered hemodynamics. Our laboratory has been exposing cultured ECs to well-defined fluid mechanical forces and identifying intracellular redox-sensitive signaling pathways that determine cell (dys)function and fate.
Earlier work provided the first evidence that arterial-level steady laminar shear stress (SS) regulates the EC mitochondrial function: SS-induced production of the vasodilator nitric oxide inhibited the electron transport chain complex activities and led to generation of mitochondrial superoxide and other reactive oxygen species (ROS). Mitochondrial ROS upregulated antioxidant genes, thus protecting ECs from oxidative stress. When SS was preceded by simulated ischemia, it resulted in excessive levels of mitochondrial ROS, mitochondrial fragmentation/fission, and EC inflammation/dys-function.
In more recent work, we determined the role of mito-chondria in shaping the SS-induced intracellular Ca2+ response: Knockdown of the Mitochondrial Ca2+ Uniporter (MCU; channel protein of the MCU complex that mediates mitochondrial Ca2+ uptake) inhibited the intracellular Ca2+ oscillations in SS-exposed ECs, suggesting that the mitochondrial Ca2+ transport is essential for shear-induced Ca2+signaling. Our current work focuses on characterizing the effects of atheroprotective vs. atheroprone flows on MCU expression/activity, mitochondrial Ca2+/ROS, and EC inflammation/dysfunction, in order to identify new molecular targets for prevention of EC dysfunction, the earliest event in cardiovascular diseases. Additional projects examine the intracellular signaling under more complex mechanical environments and during cell senescence, in order to better understand the EC dysfunction in heart failure with preserved ejection fraction.
Dr. Alevriadou received her PhD in Chemical Engineering (Bioengineering & Biosciences Institute) from Rice University, Houston, TX in 1992. Following postdoctoral training in the Department of Molecular & Experimental Medicine at Scripps Research Institute, La Jolla, CA, she joined the BME Department of Johns Hopkins University, Baltimore, MD, as Assistant Professor. In 2003, she joined the BME Center (BME Department in 2008) at the Ohio State University as Associate Professor of BME and Internal Medicine/Cardiovascular Medicine. In 2019, she joined the University at Buffalo – The State University of New York as Empire Innovation Professor in BME. Her expertise lies in vascular mechanobiology, endothelial mechanotransduction, and free radical/mitochondrial biology; understanding the role of the mechanochemical environment on cellular/molecular mechanisms of cardiovascular diseases, such as atherosclerosis and ischemia/reperfusion injury. Her research is/has been supported by the NIH and AHA. Dr. Alevriadou is a member of the Biomedical Engineering Society (Board of Directors, 2014-2017), Society for Redox Biology & Medicine, North American Vascular Biology Organization, American Physiological Society, and AHA. She reviews for federal/local funding agencies and biomedical/cardiovascular journals, and is Associate Editor of the American Journal of Physiology-Cell Physiology.