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Engineering | School of Biological and Health Systems Engineering

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Date/Time
Date(s) - 11/12/2021
3:05 pm - 4:05 pm

Category(ies)


Endothelial Mechanobiology: May the Flow Be With You

Speaker:
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

Seminar Flier

Abstract

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.

BioSketch

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.