HCMV-IE2 promotes atherosclerosis by inhibiting vascular smooth muscle cells' pyroptosis

Guixin Ma; Zhongjie Yu; Fulong Nan; Xianjuan Zhang; Shasha Jiang; Yunyang Wang; Bin Wang

doi:10.3389/fmicb.2023.1177391

HCMV-IE2 promotes atherosclerosis by inhibiting vascular smooth muscle cells' pyroptosis

Front Microbiol. 2023 May 10:14:1177391. doi: 10.3389/fmicb.2023.1177391. eCollection 2023.

Authors

Guixin Ma¹, Zhongjie Yu², Fulong Nan², Xianjuan Zhang¹, Shasha Jiang¹, Yunyang Wang³, Bin Wang^{1

2}

Affiliations

¹ Department of Pathogenic Biology, School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, China.
² Department of Special Medicine, School of Basic Medicine, Qingdao Medical College, Qingdao University, Qingdao, Shandong, China.
³ Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Abstract

Atherosclerosis is still the main cause of death in developed and developing countries. Vascular smooth muscle cells (VSMCs) death disorder is a key pathogens of atherosclerosis. During the early stage of human cytomegalovirus (HCMV) infection, immediate early protein 2 (IE2) is critical in regulating its host cell death to ensure HCMV replication. Abnormal cell death induced by HCMV infection contributes to the development of numerous diseases, including atherosclerosis. Hitherto, the underlying mechanism of HCMV involved in the progression of atherosclerosis is still unclear. In this study, the infection models in vitro and in vivo were constructed to explore the pathogenesis of HCMV-related atherosclerosis. Our results indicated that HCMV could contribute to the progression of atherosclerosis by enhancing the proliferation, invasion, and inhibiting the pyroptosis of VSMCs under inflammatory conditions. Meanwhile, IE2 played a key role in these events. Our present research revealed a novel pathogenesis of HCMV-related atherosclerosis, which might help develop new therapeutic strategies.

Keywords: HCMV; IE2; VSMCs; atherosclerosis; pyroptosis.