Department of Myocardial Pathology, Tomsk National Research Medical Center of the Russian Academy of Sciences, Cardiology Research Institute, Tomsk, Russian Federation.
Department of Pathological Physiology and Clinical Pathophysiology, Novosibirsk State Medical University, Novosibirsk, Russian Federation.
Cardiology. 2021;146(3):315-323. doi: 10.1159/000512771. Epub 2021 Feb 17.
Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases.
心血管疾病仍然是导致死亡的主要原因，占所有死亡人数的 40%，但目前癌症是全球主要的死亡原因。蒽环类药物是乳腺癌女性化疗的基石。然而，其临床应用受到其心脏毒性作用的限制，这些作用可能引发心力衰竭的发展。化疗的血管毒性可能与内皮功能障碍有关，因为蒽环类药物对内皮细胞的损伤会导致心肌病的发展和进展，减少内皮因子的释放和活性，最终导致内皮细胞死亡。这些过程抑制了抗炎和血管修复功能，并启动了未来心血管事件的发展。最近的研究表明，化疗可能会在患有已诊断心血管疾病的患者中诱导血管内皮毒性，并伴有全身内皮功能障碍。由于最初的内皮细胞损伤可能无症状，因此在多柔比星治疗结束和血管紊乱发生之间通常存在很长的延迟。在这种情况下，遗传易感性因素将有助于未来识别易感患者。本研究的目的是评估分子（内皮素-1）和遗传因素（内皮型一氧化氮合酶（NOS3，rs1799983）、内皮素-1 受体 A（EDNRA，C+70G，rs5335）和 NADPH 氧化酶（C242T，rs4673）基因多态性）在无心血管疾病的女性中内皮功能障碍和蒽环类药物诱导的心脏毒性发展中的预后作用。
