title: Fluid Mechanical Forces and Endothelial Mitochondria: A Bioengineering Perspective.
abstract: Endothelial cell dysfunction is the hallmark of every cardiovascular disease/condition, including atherosclerosis and ischemia/reperfusion injury. Fluid shear stress acting on the vascular endothelium is known to regulate cell homeostasis. Altered hemodynamics is thought to play a causative role in endothelial dysfunction. The dysfunction is associated with/preceded by mitochondrial oxidative stress. Studies by our group and others have shown that the form and/or function of the mitochondrial network are affected when endothelial cells are exposed to shear stress in the absence or presence of additional physicochemical stimuli. The present review will summarize the current knowledge on the interconnections among intracellular Ca2+- nitric oxide - mitochondrial reactive oxygen species, mitochondrial fusion/fission, autophagy/mitophagy, and cell apoptosis vs. survival. More specifically, it will list the evidence on potential regulation of the above intracellular species and processes by the fluid shear stress acting on the endothelium under either physiological flow conditions or during reperfusion (following a period of ischemia). Understanding how the local hemodynamics affects mitochondrial physiology and the cell redox state may lead to development of novel therapeutic strategies for prevention or treatment of the endothelial dysfunction and, hence, of cardiovascular disease.
authors.affiliation: Laboratory of Vascular Mechanotransduction & Oxidative Stress, Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210 ; Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Scheitlin
authors.affiliation: Laboratory of Vascular Mechanotransduction & Oxidative Stress, Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210 ; Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210.
authors.forename: Devi M
authors.initials: DM
authors.lastname: Nair
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210 ; Department of Surgery, Division of Cardiac Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Crestanello
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210 ; Department of Internal Medicine, Division of Cardiovascular Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
authors.affiliation: Laboratory of Vascular Mechanotransduction & Oxidative Stress, Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210 ; Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210 ; Department of Internal Medicine, Division of Cardiovascular Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210.
authors.forename: B Rita
authors.initials: BR
authors.lastname: Alevriadou
keywords: Shear stress; autophagy; cardiovascular disease; endothelial dysfunction; ischemia/reperfusion; mitochondrial fission; mitophagy; nitric oxide; oxidative stress; reactive oxygen species