Department of Pharmacology of Cellular Signaling Systems and Experimental Therapy, Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, 14 Eugene Pottier Street, Kiev 03068, Ukraine.
Department of Pharmacology, New York Medical College, 15 Dana Road, Valhalla 10595, NY, United States.
Biochem Pharmacol. 2019 Jan;159:121-139. doi: 10.1016/j.bcp.2018.11.019. Epub 2018 Nov 30.
Ionizing radiation (IR) leads to a variety of the cardiovascular diseases, including the arterial hypertension. A number of studies have demonstrated that blood vessels represent important target for IR, and the endothelium is one of the most vulnerable components of the vascular wall. IR causes an inhibition of nitric oxide (NO)-mediated endothelium-dependent vasodilatation and generation of reactive oxygen (ROS) and nitrogen (RNS) species trigger this process. Inhibition of NO-mediated vasodilatation could be due to endothelial NO synthase (eNOS) down-regulation, inactivation of endothelium-derived NO, and abnormalities in diffusion of NO from the endothelial cells (ECs) leading to a decrease in NO bioavailability. Beside this, IR suppresses endothelial large conductance Ca-activated K channels (BK) activity, which control NO synthesis. IR also leads to inhibition of the BK current in vascular smooth muscle cells (SMCs) which is mediated by protein kinase C (PKC). On the other hand, IR-evoked enhanced vascular contractility may result from PKC-mediated increase in SMCs myofilament Ca sensitivity. Also, IR evokes vascular wall inflammation and atherosclerosis development. Vascular function damaged by IR can be effectively restored by quercetin-filled phosphatidylcholine liposomes and mesenchymal stem cells injection. Using RNA-interference technique targeted to different PKC isoforms can also be a perspective approach for pharmacological treatment of IR-induced vascular dysfunction.
电离辐射（IR）可导致多种心血管疾病，包括动脉高血压。许多研究表明，血管是 IR 的重要靶标，而内皮细胞是血管壁最脆弱的组成部分之一。IR 会抑制一氧化氮（NO）介导的内皮依赖性血管舒张，并产生活性氧（ROS）和活性氮（RNS）物质触发这一过程。NO 介导的血管舒张抑制可能是由于内皮型一氧化氮合酶（eNOS）下调、内皮衍生的 NO 失活以及 NO 从内皮细胞（ECs）扩散的异常，导致 NO 生物利用度降低。除此之外，IR 还抑制内皮大电导钙激活钾通道（BK）的活性，该通道控制着 NO 的合成。IR 还会导致血管平滑肌细胞（SMCs）中 BK 电流的抑制，这是由蛋白激酶 C（PKC）介导的。另一方面，IR 引起的血管收缩性增强可能是由于 PKC 介导的 SMCs 肌丝 Ca 敏感性增加所致。此外，IR 还会引发血管壁炎症和动脉粥样硬化的发展。IR 损伤的血管功能可以通过填充有槲皮素的磷脂酰胆碱脂质体和间充质干细胞注射来有效恢复。针对不同 PKC 同工型的 RNA 干扰技术也可能成为治疗 IR 诱导的血管功能障碍的一种有前景的方法。
