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Endothelial Mechanobiology To Understand Cardiovascular Health and Disease

Wednesday, October 31, 2018

4:00 PM-5:30 PM

BIOMED Seminar

Endothelial Mechanobiology To Understand Cardiovascular Health and Disease

B. Rita Alevriadou, PhD
Associate Professor, Cardiovascular Medicine
Associate Professor, Biomedical Engineering
Department of Biomedical Engineering
The Ohio State University

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.

Our earlier work provided the first evidence that arterial-level steady laminar shear stress regulates the EC mitochondrial function: Shear-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.

Since reperfusion (RP)-induced EC injury following myocardial infarction is known to occur due to oxidative stress, we simulated RP as flow of oxygenated media over ischemic ECs and showed that RP leads to excessive levels of mitochondrial ROS, mitochondrial fragmentation/fission, and EC inflammation/dysfunction (our work set the standard for how to simulate in vitro ischemia/RP and quantify mitochondrial dynamics).

More recently, we determined the role of mitochondria in shaping the shear-induced intracellular Ca2+ response: Knockdown of the Mitochondrial Ca2+ Uniporter (MCU; key protein of channel that mediates mitochondrial Ca2+ uptake) inhibited the Ca2+ oscillations in sheared ECs, suggesting that mitochondrial Ca2+ transport is essential for shear-induced Ca2+signaling. Current work focuses on characterizing the effects of different physiological flows on MCU expression/activity, Ca2+/ROS signaling, EC inflammation/dysfunction, and in vivo atherosclerosis development. Despite all medical progress made, atherosclerotic vascular disease continues to be the major cause of death in developed nations. Our mechanobiology studies have the potential to identify new molecular targets for prevention of cardio-vascular diseases, including atherosclerosis, at their earliest stage of EC dysfunction.

Dr. Alevriadou, originally from Greece, received her PhD in Chemical Engineering (Bioengineering and Biosciences Institute) from Rice University, Houston, TX in 1992. Following postdoctoral training in the Department of Molecular and Experimental Medicine of the Scripps Research Institute, La Jolla, CA, she joined the BME Department of the Johns Hopkins University, Baltimore, MD, as Assistant Professor. In 2003, she joined the BME Center (since 2008, Department) and the Davis Heart & Lung Research Institute at the Ohio State University, Columbus, OH, as Associate Professor of BME and Internal Medicine, Cardiovascular Medicine.

Dr. Alevriadou’s expertise lies in cardiovascular bioengineering, endothelial mechanotransduction, and free radical/mitochondrial biology; in general, understanding the molecular basis of cardiovascular diseases (atherosclerosis, ischemia/reperfusion injury, diabetes). Her research has been/is supported by the NIH and AHA. At OSU, she is a member of the Biomedical Sciences and Biophysics graduate programs and the Center for Regenerative Medicine & Cell-Based Therapies. At the national level, she is a member of BMES (an elected member on the Board of Directors, 2014-17; and member of the Student Affairs and Diversity Committees, 2015-present), North American Vascular Biology Organization, Society for Redox Biology and Medicine, and AHA. She regularly reviews for federal and local funding agencies (NIH, AHA, NSF) and biomedical/cardiovascular journals, and also serves on the Editorial Board of the American Journal of Physiology-Cell Physiology (2002-present).

Contact Information

Ken Barbee

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Papadakis Integrated Sciences Building (PISB), Room 120, located on the northeast corner of 33rd and Chestnut Streets.


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