Pathology and biology of radiation-induced cardiac disease

Abstract

Heart disease is the leading global cause of death. The risk for this disease is significantly increased in populations exposed to ionizing radiation, but the mechanisms are not fully elucidated yet. This review aims to gather and discuss the latest data about pathological and biological consequences in the radiation-exposed heart in a comprehensive manner. A better understanding of the molecular and cellular mechanisms underlying radiation-induced damage in heart tissue and cardiac vasculature will provide novel targets for therapeutic interventions. These may be valuable for individuals clinically or occupationally exposed to varying doses of ionizing radiation.

Keywords: cardiac disease; endothelial cell; heart; ionizing radiation; myocardium.

Fig. 1.

Proposed model of the biological pathways in cardiomyocytes, smooth muscle cells (SMCs) and endothelial cells involved in radiation-induced heart disease. In cardiomyocytes, the inactivation of PPAR alpha, reduced fatty acid oxidation (FAO), increased inflammatory response, and enhanced production of mitochondrial ROS are indicated. In SMCs, the adverse effects on paxillin/integrin and actin signaling, cytoskeletal organization, and cell–cell junctions are shown. In endothelial cells, the inactivation of PI3K, MAP kinase and Rho signaling pathways, increased cytoskeletal disorganization, decreased NO production and bioavailability, and enhanced leukocyte migration due to increased cell adhesion and loosening of cell–cell junctions are indicated.