Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis.

Qinhong Wang,Rahima Zennadi

doi:10.3390/ijms21124259

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.

Highlights

Aging contributes to an elevated incidence of venous thrombosis (VT)/thromboembolism (VT/E) [1,2], the third most common cause of cardiovascular death worldwide
We will mainly focus on the valuable role of the red blood cell (RBC) in oxidative stress-related thrombotic processes, and how oxidative stress within the RBC affects RBC quality and function, which contribute to the development of thrombosis during aging
Oxidative stress-associated endothelial injury may be triggered by elevated reactive oxygen species (ROS) levels in RBCs during aging, since the RBC is a major source of ROS production and oxidative stress

Summary

Introduction

Aging contributes to an elevated incidence of venous thrombosis (VT)/thromboembolism (VT/E) [1,2], the third most common cause of cardiovascular death worldwide. The coagulation process is under the inhibitory control of several inhibitors that limit clot formation, thereby avoiding thrombus propagation This delicate balance is interrupted whenever the procoagulant activity of the coagulation factors is increased, or the activity of naturally occurring inhibitors is decreased. Aging is associated with overproduction of reactive oxygen species (ROS), which could evoke a series of physiological changes that create a discrepancy between thrombosis and hemorrhage [6,7,8,9]. These pathophysiologic changes involve anomalies in blood coagulability, including vessel function [10,11], blood flow, and the coagulation pathways [12]. The summarized information will highlight useful knowledge of the role of oxidative stress in RBCs in precipitating thrombotic events in relation to aging

Oxidative Stress Contribution to Venous Thrombosis during Aging

RBC Oxidative Stress and Its Effect on RBC Quality during Aging

Oxidative Stress in RBCs and Its Effect on Venous Thrombosis during Aging

RBCs as a Major Source of Oxidative Stress-Associated Thrombosis during Aging

Genetic Risk Factors and Venous Thrombosis

Conclusions