Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis.
Abstract
Mid-life stage adults are at higher risk of developing venous thrombosis (VT)/thromboembolism
(VT/E). Aging is characterized by an overproduction of reactive oxygen species (ROS),
which could evoke a series of physiological changes involved in thrombosis. Here,
we focus on the critical role of ROS within the red blood cell (RBC) in initiating
venous thrombosis during aging. Growing evidence has shifted our interest in the role
of unjustifiably unvalued RBCs in blood coagulation. RBCs can be a major source of
oxidative stress during aging, since RBC redox homeostasis is generally compromised
due to the discrepancy between prooxidants and antioxidants. As a result, ROS accumulate
within the RBC due to the constant endogenous hemoglobin (Hb) autoxidation and NADPH
oxidase activation, and the uptake of extracellular ROS released by other cells in
the circulation. The elevated RBC ROS level affects the RBC membrane structure and
function, causing loss of membrane integrity, and decreased deformability. These changes
impair RBC function in hemostasis and thrombosis, favoring a hypercoagulable state
through enhanced RBC aggregation, RBC binding to endothelial cells affecting nitric
oxide availability, RBC-induced platelet activation consequently modulating their
activity, RBC interaction with and activation of coagulation factors, increased RBC
phosphatidylserine exposure and release of microvesicles, accelerated aging and hemolysis.
Thus, RBC oxidative stress during aging typifies an ultimate mechanism in system failure,
which can affect major processes involved in the development of venous thrombosis
in a variety of ways. The reevaluated concept of the critical role of RBC ROS in the
activation of thrombotic events during aging will help identify potential targets
for novel strategies to prevent/reduce the risk for VT/E or VT/E recurrences in mid-life
stage adults.
Type
Journal articleSubject
VT/Eaging
antioxidant defenses
oxidative stress
reactive oxygen species
red blood cell
redox regulation
venous thrombosis
Aging
Blood Coagulation Factors
Erythrocytes
Hemostasis
Humans
Oxidative Stress
Phosphatidylserines
Reactive Oxygen Species
Venous Thrombosis
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https://hdl.handle.net/10161/22406Published Version (Please cite this version)
10.3390/ijms21124259Publication Info
Wang, Qinhong; & Zennadi, Rahima (2020). Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs
in Venous Thrombosis. International journal of molecular sciences, 21(12). pp. 1-22. 10.3390/ijms21124259. Retrieved from https://hdl.handle.net/10161/22406.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Rahima Zennadi
Associate Professor in Medicine
My research in Hematology addresses three areas of investigation: disorders associated
with sickle cell disease pathophysiology, venous thrombosis/thromboembolism (VT/E)
associated with aging, and cerebrovascular injury.
In sickle cell disease, vaso-occlusion leads to serious life-threatening complications,
including acute pain crises and irreversible organ damage. Vaso-occlusion is caused
largely by sickle red blood cell adhesion to the vascular endothelium. Prevention
of

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