An integrative review of nonobvious puzzles of cellular and molecular cardiooncology

Abstract

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of cancer survivors and their increased morbidity and mortality. Cellular and molecular determinants of these relations are far less understood, mainly because of several unsolved paths and contradicting findings in the literature. In this article, we provide a comprehensive view of the cellular and molecular etiology of cardiooncology. We pay particular attention to various intracellular processes that arise in cardiomyocytes, vascular endothelial cells, and smooth muscle cells treated in experimentally-controlled conditions in vitro and in vivo with ionizing radiation and drugs representing diverse modes of anti-cancer activity.

Keywords: Cardiac cells; Cardiooncology; Cardiotoxicity; Vascular cells.

Fig. 1

Pathomechanisms of IR-dependent cardio- and vasotoxicity in cardiomyocytes (A), vascular endothelial cells (B), and vascular smooth muscle cells (C). AC acetylation, Me methylation, SM sphingomyelin, OONO⁻ peroxynitrite, aSMase acid sphingomyelinase, PIP₃ phosphatidylinositol (3,4,5)-trisphosphate, PLC phospholipase C, DAG diacylglycerol, IP₃ inositol 1,4,5-trisphosphate, IP₃-R inositol 1,4,5-trisphosphate receptor

Fig. 2

Pathomechanisms of anthracycline-dependent cardio- and vasotoxicity in cardiomyocytes (A), vascular endothelial cells (B), and vascular smooth muscle cells (C). ER endoplasmic reticulum, SR sarcoplasmic reticulum, α1AR α_1A-adrenoceptor, CLOCK Clock gene