Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection

被引:25
作者
Brumback, Brittany D. [1 ,2 ]
Dmytrenko, Oleksandr [1 ]
Robinson, Ashley N. [1 ]
Bailey, Adam L. [3 ,4 ]
Ma, Pan [1 ]
Liu, Jing [1 ]
Hicks, Stephanie C. [1 ]
Ng, Sherwin [1 ]
Li, Gang [1 ,2 ]
Zhang, David M. [1 ]
Lipovsky, Catherine E. [1 ,5 ]
Lin, Chieh-Yu [3 ]
Diamond, Michael S. [3 ,6 ,7 ]
Lavine, Kory J. [1 ,3 ,5 ]
Rentschler, Stacey L. [1 ,2 ,5 ,8 ]
机构
[1] Washington Univ, Cardiovasc Div, Dept Med, St Louis, MO USA
[2] Washington Univ, Dept Biomed Engn, St Louis, MO USA
[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA
[4] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA
[5] Washington Univ, Dept Dev Biol, St Louis, MO USA
[6] Washington Univ, Sch Med, Dept Med, Infect Dis, St Louis, MO USA
[7] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA
[8] Washington Univ, Sch Med, Dept Med, Cardiovasc Div, 309 McDonnell Sci Bldg, Campus POB 8103,660 South, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
cardiovascular disease; COVID-19; pericytes; SARS-CoV-2; ENDOTHELIAL DYSFUNCTION; COVID-19;
D O I
10.1016/j.jacbts.2022.09.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.
引用
收藏
页码:109 / 120
页数:12
相关论文
共 29 条
[21]   Microthrombi as a Major Cause of Cardiac Injury in COVID-19 A Pathologic Study [J].
Pellegrini, Dario ;
Kawakami, Rika ;
Guagliumi, Giulio ;
Sakamoto, Atsushi ;
Kawai, Kenji ;
Gianatti, Andrea ;
Nasr, Ahmed ;
Kutys, Robert ;
Guo, Liang ;
Cornelissen, Anne ;
Faggi, Lara ;
Mori, Masayuki ;
Sato, Yu ;
Pescetelli, Irene ;
Brivio, Matteo ;
Romero, Maria ;
Virmani, Renu ;
Finn, Aloke V. .
CIRCULATION, 2021, 143 (10) :1031-1042
[22]  
Pipelines R&D, 2020, COVID 19 ARTIC V3 IL, DOI 10.17504/protocols.io.bgxjjxkn
[23]   Role of angiotensin-converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection [J].
Robinson, Fulton A. ;
Mihealsick, Ryan P. ;
Wagener, Brant M. ;
Hanna, Peter ;
Poston, Megan D. ;
Efimov, Igor R. ;
Shivkumar, Kalyanam ;
Hoover, Donald B. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2020, 319 (05) :H1059-H1068
[24]   Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research [J].
Simmons, Graham ;
Zmora, Pawel ;
Gierer, Stefanie ;
Heurich, Adeline ;
Poehlmann, Stefan .
ANTIVIRAL RESEARCH, 2013, 100 (03) :605-614
[25]   Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19 [J].
Sims, Jonathan T. ;
Krishnan, Venkatesh ;
Chang, Ching-Yun ;
Engle, Sarah M. ;
Casalini, Giacomo ;
Rodgers, George H. ;
Bivi, Nicoletta ;
Nickoloff, Brian J. ;
Konrad, Robert J. ;
de Bono, Stephanie ;
Higgs, Richard E. ;
Benschop, Robert J. ;
Ottaviani, Silvia ;
Cardoso, Anabela ;
Nirula, Ajay ;
Corbellino, Mario ;
Stebbing, Justin .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2021, 147 (01) :107-111
[26]   A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope [J].
VanBlargan, Laura A. ;
Adams, Lucas J. ;
Liu, Zhuoming ;
Chen, Rita E. ;
Gilchuk, Pavlo ;
Raju, Saravanan ;
Smith, Brittany K. ;
Zhao, Haiyan ;
Case, James Brett ;
Winkler, Emma S. ;
Whitener, Bradley M. ;
Droit, Lindsay ;
Aziati, Ishmael D. ;
Bricker, Traci L. ;
Joshi, Astha ;
Shi, Pei-Yong ;
Creanga, Adrian ;
Pegu, Amarendra ;
Handley, Scott A. ;
Wang, David ;
Boon, Adrianus C. M. ;
Crowe, James E., Jr. ;
Whelan, Sean P. J. ;
Fremont, Daved H. ;
Diamond, Michael S. .
IMMUNITY, 2021, 54 (10) :2399-+
[27]   A human three-dimensional neural-perivascular 'assembloid' promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology [J].
Wang, Lu ;
Sievert, David ;
Clark, Alex E. ;
Lee, Sangmoon ;
Federman, Hannah ;
Gastfriend, Benjamin D. ;
Shusta, Eric V. ;
Palecek, Sean P. ;
Carlin, Aaron F. ;
Gleeson, Joseph G. .
NATURE MEDICINE, 2021, 27 (09) :1600-+
[28]   An Infectious cDNA Clone of SARS-CoV-2 [J].
Xie, Xuping ;
Muruato, Antonio ;
Lokugamage, Kumari G. ;
Narayanan, Krishna ;
Zhang, Xianwen ;
Zou, Jing ;
Liu, Jianying ;
Schindewolf, Craig ;
Bopp, Nathen E. ;
Aguilar, Patricia, V ;
Plante, Kenneth S. ;
Weaver, Scott C. ;
Makino, Shinji ;
LeDuc, James W. ;
Menachery, Vineet D. ;
Shi, Pei-Yong .
CELL HOST & MICROBE, 2020, 27 (05) :841-+
[29]   TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes [J].
Zang, Ruochen ;
Castro, Maria Florencia Gomez ;
McCune, Broc T. ;
Zeng, Qiru ;
Rothlauf, Paul W. ;
Sonnek, Naomi M. ;
Liu, Zhuoming ;
Brulois, Kevin F. ;
Wang, Xin ;
Greenberg, Harry B. ;
Diamond, Michael S. ;
Ciorba, Matthew A. ;
Whelan, Sean P. J. ;
Ding, Siyuan .
SCIENCE IMMUNOLOGY, 2020, 5 (47)