Rastogi Mukul, Sarkar Subendu, Makol Ankita, Sandip Singh Rana, Saikia Uma Nahar, Banerjee Dibyajyoti, Chopra Seema, Chakraborti Anuradha
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Department of Cardiothoracic and Vascular Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Genes Dis. 2018 Feb 13;5(3):275-289. doi: 10.1016/j.gendis.2018.02.002. eCollection 2018 Sep.
Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in developing nations like India. RHD commonly affects the mitral valve which is lined by a single layer of endothelial cells (ECs). The role of ECs in mitral valve damage during RHD is not well elucidated. In here, anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs (HUVECs and HMVECs). ECs proinflammatory phenotype with increased expression of TNFα, IL-6, IL-8, IFNγ, IL-1β, ICAM1, VCAM1, E-selectin, laminin B, and vimentin was documented in both ECs. The promoter hypomethylation of various key inflammatory cytokines (TNFα, IL-6, and IL-8), integrin (ICAM1) associated with leukocyte transendothelial migration, and extracellular matrix genes (vimentin, and laminin) were also observed. Further, the data was in accordance with observations which correlated significantly with the etiological factors such as smoking, socioeconomic status, and housing. Thus, the study sheds light on the role of ECs in RHD which is a step forward in the elucidation of disease pathogenesis.
风湿性心脏病（RHD）是印度等发展中国家心血管疾病发病率和死亡率的主要原因。RHD通常影响二尖瓣，其由单层内皮细胞（ECs）衬里。ECs在RHD期间二尖瓣损伤中的作用尚未得到充分阐明。在此，使用来自RHD患者的抗内皮细胞抗体刺激ECs（人脐静脉内皮细胞和人二尖瓣内皮细胞）。在两种ECs中均记录到促炎表型，肿瘤坏死因子α、白细胞介素-6、白细胞介素-8、干扰素γ、白细胞介素-1β、细胞间黏附分子1、血管细胞黏附分子1、E-选择素、层粘连蛋白B和波形蛋白的表达增加。还观察到各种关键炎性细胞因子（肿瘤坏死因子α、白细胞介素-6和白细胞介素-8）、与白细胞跨内皮迁移相关的整合素（细胞间黏附分子1）以及细胞外基质基因（波形蛋白和层粘连蛋白）的启动子低甲基化。此外，该数据与吸烟、社会经济地位和住房等病因因素显著相关的观察结果一致。因此，该研究阐明了ECs在RHD中的作用，这是在阐明疾病发病机制方面向前迈出的一步。
