Li Rui, Zhang Yuan, Yan Huacheng, Xiao Hua, Ruan Yunjun, Qiu Jian, Shi Lei
Department of Cardiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
Mol Med Rep. 2017 Feb;15(2):643-648. doi: 10.3892/mmr.2016.6039. Epub 2016 Dec 14.
Atherosclerosis (AS) is a common pathological basis for the development of various cardiovascular and cerebrovascular diseases, however, currently, no effective treatment against AS has been established. It has previously been suggested that intravascular cytochrome P450 (CYP) oxidase is involved in the pathogenesis of AS. The present study investigated the role of cytochrome P450, family 2, subfamily J, polypeptide 2 (CYP2J2), the most common subtype of CYP oxidase in the human body, in the occurrence and development of AS. CYP2J2 was overexpressed in human umbilical vein endothelial cells (HUVECs), human arterial smooth muscle cells (HASMCs), and human peripheral monocyte‑derived foam cells by lentiviral infection. The mRNA and protein levels were measured by reverse‑transcription quantitative polymerase chain reaction and western blotting, respectively. Cell proliferation and migration were determined by MTS and Transwell assays, respectively. Furthermore, lipid accumulation was detected with Oil red O staining. The concentrations of total and free cholesterol were measured using a quantitation kit. Following lentiviral infection, CYP2J2 was successfully overexpressed in HUVEC, HASMC and foam cells. CYP2J2 overexpression promoted proliferation and migration in HUVECs and suppressed these actions in HASMCs. In addition, it suppressed oxidized low‑density lipoprotein‑induced foam cell formation. In conclusion, it was hypothesized that CYP2J2 may have a protective role in AS, as proliferation of HASMCs and the formation of foam cells are notable characteristics of AS.
动脉粥样硬化(AS)是各种心脑血管疾病发生发展的常见病理基础,然而,目前尚未建立有效的抗AS治疗方法。先前有研究表明,血管内细胞色素P450(CYP)氧化酶参与AS的发病机制。本研究探讨了人体中最常见的CYP氧化酶亚型细胞色素P450 2J亚家族2型(CYP2J2)在AS发生发展中的作用。通过慢病毒感染在人脐静脉内皮细胞(HUVECs)、人动脉平滑肌细胞(HASMCs)和人外周血单核细胞衍生的泡沫细胞中过表达CYP2J2。分别通过逆转录定量聚合酶链反应和蛋白质印迹法检测mRNA和蛋白质水平。分别通过MTS和Transwell试验测定细胞增殖和迁移。此外,用油红O染色检测脂质蓄积。使用定量试剂盒测量总胆固醇和游离胆固醇的浓度。慢病毒感染后,CYP2J2在HUVEC、HASMC和泡沫细胞中成功过表达。CYP2J2过表达促进HUVECs的增殖和迁移,并抑制HASMCs中的这些作用。此外,它抑制氧化低密度脂蛋白诱导的泡沫细胞形成。总之,据推测CYP2J2可能在AS中具有保护作用,因为HASMCs的增殖和泡沫细胞的形成是AS的显著特征。