Radiation-Induced Endothelial Vascular Injury: A Review of Possible Mechanisms

Bhanu Prasad Venkatesulu, Lakshmi Shree Mahadevan, Maureen L Aliru, Xi Yang, Monica Himaani Bodd, Pankaj K Singh, Syed Wamique Yusuf, Jun-Ichi Abe, Sunil Krishnan, Bhanu Prasad Venkatesulu, Lakshmi Shree Mahadevan, Maureen L Aliru, Xi Yang, Monica Himaani Bodd, Pankaj K Singh, Syed Wamique Yusuf, Jun-Ichi Abe, Sunil Krishnan

Abstract

In radiation therapy for cancer, the therapeutic ratio represents an optimal balance between tumor control and normal tissue complications. As improvements in the therapeutic arsenal against cancer extend longevity, the importance of late effects of radiation increases, particularly those caused by vascular endothelial injury. Radiation both initiates and accelerates atherosclerosis, leading to vascular events like stroke, coronary artery disease, and peripheral artery disease. Increased levels of proinflammatory cytokines in the blood of long-term survivors of the atomic bomb suggest that radiation evokes a systemic inflammatory state responsible for chronic vascular side effects. In this review, the authors offer an overview of potential mechanisms implicated in radiation-induced vascular injury.

Keywords: ATM, ataxia telangiectasia mutated; CD, cluster of differentiation; EC, endothelial cell; HUVEC, human umbilical vein endothelial cell; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; LDL, low-density lipoprotein; MAPK, mitogen-activated protein kinase; NEMO, nuclear factor kappa B essential modulator; NF-κB, nuclear factor-kappa beta; ROS, reactive oxygen species; SEK1, stress-activated protein kinase 1; TNF, tumor necrosis factor; XIAP, X-linked inhibitor of apoptosis; angiogenesis; apoptosis; cytokines; mTOR, mammalian target of rapamycin; senescence.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
Proposed Interplay Between Apoptosis and Endothelial Senescence and Its Implications for Pathogenesis ATM = ataxia telangiectasia mutated; b-FGF = basic fibroblast growth factor; ERK = extracellular signal-regulated kinase; IGF = insulin-like growth factor; LDL = low-density lipoprotein; MAPK = mitogen-activated protein kinase; SASP = senescence-associated secretory phenotype; SEK1 = stress-activated protein kinase 1; TNF = tumor necrosis factor.
Figure 2
Figure 2
Possible Mechanisms Implicated in Radiation-Induced Vascular Injury CAD = coronary artery disease; CNS = central nervous system; CVA = cerebrovascular accident; CXCL = chemokine ligand; IGFBP-5 = insulin-like growth factor binding protein; NEMO = nuclear factor kappa B essential modulator; PAD = peripheral artery disease; PAI = plasminogen activator inhibitor; SMA = smooth muscle actin; SPRY = sprout homolog; TLR = Toll-like receptor; vWF = von Willebrand factor; XIAP = X-linked inhibitor of apoptosis.
Central Illustration
Central Illustration
Changes That Occur in Vasculature After Radiation Exposure IL = interleukin; TNF = tumor necrosis factor; vWF = von Willebrand factor.

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