SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice

作     者：Yuanwu Ma Dan Lu Linlin Bao Yajin Qu Jiangning Liu Xiaolong Qi Lei Yu Xu Zhang Feifei Qi Qi Lv Yunpeng Liu Xudong Shi Caixian Sun Jing Li Jie Wang Yunlin Han Kai Gao Wei Dong Ning Liu Shan Gao Jing Xue Qiang Wei Sidan Pan Hong Gao Lianfeng Zhang Chuan Qin Yuanwu Ma;Dan Lu;Linlin Bao;Yajin Qu;Jiangning Liu;Xiaolong Qi;Lei Yu;Xu Zhang;Feifei Qi;Qi Lv;Yunpeng Liu;Xudong Shi;Caixian Sun;Jing Li;Jie Wang;Yunlin Han;Kai Gao;Wei Dong;Ning Liu;Shan Gao;Jing Xue;Qiang Wei;Sidan Pan;Hong Gao;Lianfeng Zhang;Chuan Qin

作者机构：Key Laboratory of Human Disease Comparative MedicineNational Health Commission of China(NHC)Institute of Laboratory Animal SciencePeking Union Medicine CollegeChinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencePeking Union Medicine CollegeChinese Academy of Medical SciencesBeijingChina 

出 版 物：《Animal Models and Experimental Medicine》 (动物模型与实验医学（英文）)

年 卷 期：2021年第4卷第1期

页      面：2-15页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：National Natural Science Foundation of China,Grant/Award Number:82041008 and 32070543 National Mega Projects of China for Major Infectious Diseases,Grant/Award Number:2017ZX10304402 CAMS Initiative for Innovative Medicine of China,Grant/Award Number:2016-12M-2-006 and 2017-12M-3-015 Beijing Municipal Natural Science Foundation,Grant/Award Number:M21004。 

主　　题：Cardiovascular disease COVID-19 diabetes mellitus mouse model SARS-CoV-2 

摘      要：Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.