Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Clinical Laboratory, The Second People's Hospital of Hefei, China.
Adv Clin Exp Med. 2019 Nov;28(11):1441-1450. doi: 10.17219/acem/109199.
Human cytomegalovirus (HCMV) infection is one of the risk factors of cardiovascular disease; the most important pathological change is the change of vascular endothelial cell (VEC) function, but its mechanism is still unclear. Transforming growth factor β1 (TGF-β1) is an important cytokine associated with fibrosis; it can induce the occurrence of endothelial mesenchymal transition (EndMT) in VECs, which means endothelial cells acquire the characteristics and phenotypes of mesenchymal cells and secrete molecules associated with the deposition and remodeling of the extracellular matrix. Many in vivo and in vitro studies have shown that HCMV infection promotes the secretion and activation of TGF-β1.
This study aims to observe the changes of endothelial cells after HCMV infection and EndMT occurrence induced by TGF-β1 and to explore the possible mechanism of HCMV infection in the pathogenesis of cardiovascular disease.
Immunofluorescence staining, reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation methods were used in this study to analyze the changes in morphology and gene expression.
We found that EndMT-related morphological and gene expression changes occurred in human umbilical vein endothelial cells (HUVECs) infected and uninfected with HCMV after treatment with TGF-β1. Human umbilical vein endothelial cells infected with HCMV, which are treated with TGF-β1, can activate the extracellular potential TGF-β1 by activating matrix metalloproteinase 2 (MMP-2).
Our findings provide a molecular basis for the association between HCMV infection, TGF-β1 and cardiovascular disease.
人巨细胞病毒（HCMV）感染是心血管疾病的危险因素之一；其最重要的病理改变是血管内皮细胞（VEC）功能的改变，但具体机制尚不清楚。转化生长因子β1（TGF-β1）是与纤维化相关的重要细胞因子；它可以诱导 VEC 发生内皮间质转化（EndMT），即内皮细胞获得间充质细胞的特征和表型，并分泌与细胞外基质沉积和重塑相关的分子。许多体内和体外研究表明，HCMV 感染可促进 TGF-β1 的分泌和激活。
本研究旨在观察 HCMV 感染后 TGF-β1 诱导的内皮细胞变化和 EndMT 的发生，并探讨 HCMV 感染在心血管疾病发病机制中的可能机制。
本研究采用免疫荧光染色、逆转录聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和免疫沉淀方法分析形态学和基因表达的变化。
我们发现，TGF-β1 处理后，HCMV 感染和未感染的人脐静脉内皮细胞（HUVEC）发生 EndMT 相关的形态和基因表达变化。用 TGF-β1 处理 HCMV 感染的人脐静脉内皮细胞可通过激活基质金属蛋白酶 2（MMP-2）激活细胞外 TGF-β1。
我们的研究结果为 HCMV 感染、TGF-β1 与心血管疾病之间的关联提供了分子基础。
