Radiation-Induced Endothelial Vascular Injury

Abstract

SummaryIn 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.

Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer

“…The tumor vasculature and endothelial cells are some of the most studied components to assess radiobiological effects in the tumor microenvironment following radiation treatment. It is well-characterized that radiation induces endothelial cell dysfunction, including increased permeability, detachment from the underlying basement membrane, and endothelial cell senescence and/or apoptosis (18,19). In normal brain tissue the αPD-1 immunotherapy alone increased blood vasculature while in combination with RT blood vasculature reduced.…”

The Role of NLRP3 Inflammasome in Radiation-Induced Cardiovascular Injury

“…Radiation (≥10 Gy) can induce cell cycle arrest and Bax-mediated apoptosis of endothelial progenitor cells (EPCs), and cause cellular senescence in well-differentiated ECs similar to that observed in premature atherosclerosis (Venkatesulu et al, 2018). Radiationinduced cell death, which is characterized by mitotic catastrophe, apoptosis, and senescence, could stimulate an acute reduction in capillary density or induce chronic inflammation, resulting in disruption of vascular homeostasis (Venkatesulu et al, 2018).…”

Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature

“…Despite significant advances in cancer radiation modalities, which allow for more accurate dose delivery, the therapeutic ratio of cancer radiotherapy remains limited by off‐target damages to normal tissues. In this regard, the microvasculature plays a critical role, not only because in addition to inherently influencing the overall tumor response, radiation‐induced damages to vascular cells directly or indirectly result in both acute and long‐term side effects with often severe consequences for patients . The organs and tissues most relevant to cancer radiotherapy, including the liver, kidney, gastrointestinal tract, skin, brain, and lungs, are indeed characterized by a high concentration of radiosensitive microvascular structures .…”

“…In this regard, the microvasculature plays a critical role, not only because in addition to inherently influencing the overall tumor response, radiation‐induced damages to vascular cells directly or indirectly result in both acute and long‐term side effects with often severe consequences for patients . The organs and tissues most relevant to cancer radiotherapy, including the liver, kidney, gastrointestinal tract, skin, brain, and lungs, are indeed characterized by a high concentration of radiosensitive microvascular structures . The nature of radiation induced injuries to vascular cells as well as their tissue‐specific microenvironment dictate the clinical manifestation and extent of radiological side‐effects.…”