Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection
[Display omitted] •SARS-CoV-2 infects and replicates within cardiac pericytes in human organotypic cardiac slices.•SARS-CoV-2 infects human primary cardiac pericytes through an ACE2- and endosomal-dependent pathway.•Infection of human primary cardiac pericytes leads to up-regulation of inflammatory...
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| Veröffentlicht in: | JACC. Basic to translational science 2023-02, Vol.8 (2), p.109-120 |
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| container_title | JACC. Basic to translational science |
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| creator | Brumback, Brittany D. Dmytrenko, Oleksandr Robinson, Ashley N. Bailey, Adam L. Ma, Pan Liu, Jing Hicks, Stephanie C. Ng, Sherwin Li, Gang Zhang, David M. Lipovsky, Catherine E. Lin, Chieh-Yu Diamond, Michael S. Lavine, Kory J. Rentschler, Stacey L. |
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•SARS-CoV-2 infects and replicates within cardiac pericytes in human organotypic cardiac slices.•SARS-CoV-2 infects human primary cardiac pericytes through an ACE2- and endosomal-dependent pathway.•Infection of human primary cardiac pericytes leads to up-regulation of inflammatory chemokine and cytokine expression, type I IFN signaling, mediators of vasoreactivity, and NF-κB–dependent cell death.•SARS-CoV-2 directly infects cardiac pericytes in patients with COVID-19 myocarditis.
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. |
| doi_str_mv | 10.1016/j.jacbts.2022.09.001 |
| format | Article |
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•SARS-CoV-2 infects and replicates within cardiac pericytes in human organotypic cardiac slices.•SARS-CoV-2 infects human primary cardiac pericytes through an ACE2- and endosomal-dependent pathway.•Infection of human primary cardiac pericytes leads to up-regulation of inflammatory chemokine and cytokine expression, type I IFN signaling, mediators of vasoreactivity, and NF-κB–dependent cell death.•SARS-CoV-2 directly infects cardiac pericytes in patients with COVID-19 myocarditis.
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.</description><identifier>ISSN: 2452-302X</identifier><identifier>EISSN: 2452-302X</identifier><identifier>DOI: 10.1016/j.jacbts.2022.09.001</identifier><identifier>PMID: 36124009</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>cardiovascular disease ; COVID-19 ; Leading Edge Translational Research ; pericytes ; SARS-CoV-2</subject><ispartof>JACC. Basic to translational science, 2023-02, Vol.8 (2), p.109-120</ispartof><rights>2023 The Authors</rights><rights>2023 The Authors.</rights><rights>2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-ac72ce9d365cadac6946ca54336c83113af017f4f80d33e9b253859c2a56e3303</citedby><cites>FETCH-LOGICAL-c463t-ac72ce9d365cadac6946ca54336c83113af017f4f80d33e9b253859c2a56e3303</cites><orcidid>0000-0002-1744-1238</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473702/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473702/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36124009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brumback, Brittany D.</creatorcontrib><creatorcontrib>Dmytrenko, Oleksandr</creatorcontrib><creatorcontrib>Robinson, Ashley N.</creatorcontrib><creatorcontrib>Bailey, Adam L.</creatorcontrib><creatorcontrib>Ma, Pan</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Hicks, Stephanie C.</creatorcontrib><creatorcontrib>Ng, Sherwin</creatorcontrib><creatorcontrib>Li, Gang</creatorcontrib><creatorcontrib>Zhang, David M.</creatorcontrib><creatorcontrib>Lipovsky, Catherine E.</creatorcontrib><creatorcontrib>Lin, Chieh-Yu</creatorcontrib><creatorcontrib>Diamond, Michael S.</creatorcontrib><creatorcontrib>Lavine, Kory J.</creatorcontrib><creatorcontrib>Rentschler, Stacey L.</creatorcontrib><title>Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection</title><title>JACC. Basic to translational science</title><addtitle>JACC Basic Transl Sci</addtitle><description>[Display omitted]
•SARS-CoV-2 infects and replicates within cardiac pericytes in human organotypic cardiac slices.•SARS-CoV-2 infects human primary cardiac pericytes through an ACE2- and endosomal-dependent pathway.•Infection of human primary cardiac pericytes leads to up-regulation of inflammatory chemokine and cytokine expression, type I IFN signaling, mediators of vasoreactivity, and NF-κB–dependent cell death.•SARS-CoV-2 directly infects cardiac pericytes in patients with COVID-19 myocarditis.
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.</description><subject>cardiovascular disease</subject><subject>COVID-19</subject><subject>Leading Edge Translational Research</subject><subject>pericytes</subject><subject>SARS-CoV-2</subject><issn>2452-302X</issn><issn>2452-302X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kE9P4zAQxS3EClCXb4BWOXJJGNuJE19AVcUCEhIrCoib5U4mi6s0LnaCxLffVOXvZU8z0rx5b-bH2BGHjANXJ8tsaXHRx0yAEBnoDIDvsAORFyKVIB53v_T77DDGJYwKJcuqKvbYvlRc5AD6gJ1dDivbJTMbamcx-UPB4WtPMZkGSuZDRFr3btFS0vtkPr2dpzP_kIrkqmsIe-e7n-xHY9tIh291wu5_n9_NLtPrm4ur2fQ6xVzJPrVYCiRdS1WgrS0qnSu0RS6lwkpyLm0DvGzypoJaStILUciq0ChsoUhKkBN2uvVdD4sV1UhdH2xr1sGtbHg13jrzfdK5J_PXvxidl7IEMRocvxkE_zxQ7M3Kjd-1re3ID9GIkiuo9AbShOVbKQYfY6DmI4aD2eA3S7PFbzb4DWgzwh3Xfn098WPpHfbnDzSCenEUTERHHVLtwkjT1N79P-EfuD-XCQ</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Brumback, Brittany D.</creator><creator>Dmytrenko, Oleksandr</creator><creator>Robinson, Ashley N.</creator><creator>Bailey, Adam L.</creator><creator>Ma, Pan</creator><creator>Liu, Jing</creator><creator>Hicks, Stephanie C.</creator><creator>Ng, Sherwin</creator><creator>Li, Gang</creator><creator>Zhang, David M.</creator><creator>Lipovsky, Catherine E.</creator><creator>Lin, Chieh-Yu</creator><creator>Diamond, Michael S.</creator><creator>Lavine, Kory J.</creator><creator>Rentschler, Stacey L.</creator><general>Elsevier Inc</general><general>The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1744-1238</orcidid></search><sort><creationdate>20230201</creationdate><title>Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection</title><author>Brumback, Brittany D. ; Dmytrenko, Oleksandr ; Robinson, Ashley N. ; Bailey, Adam L. ; Ma, Pan ; Liu, Jing ; Hicks, Stephanie C. ; Ng, Sherwin ; Li, Gang ; Zhang, David M. ; Lipovsky, Catherine E. ; Lin, Chieh-Yu ; Diamond, Michael S. ; Lavine, Kory J. ; Rentschler, Stacey L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-ac72ce9d365cadac6946ca54336c83113af017f4f80d33e9b253859c2a56e3303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>cardiovascular disease</topic><topic>COVID-19</topic><topic>Leading Edge Translational Research</topic><topic>pericytes</topic><topic>SARS-CoV-2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brumback, Brittany D.</creatorcontrib><creatorcontrib>Dmytrenko, Oleksandr</creatorcontrib><creatorcontrib>Robinson, Ashley N.</creatorcontrib><creatorcontrib>Bailey, Adam L.</creatorcontrib><creatorcontrib>Ma, Pan</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Hicks, Stephanie C.</creatorcontrib><creatorcontrib>Ng, Sherwin</creatorcontrib><creatorcontrib>Li, Gang</creatorcontrib><creatorcontrib>Zhang, David M.</creatorcontrib><creatorcontrib>Lipovsky, Catherine E.</creatorcontrib><creatorcontrib>Lin, Chieh-Yu</creatorcontrib><creatorcontrib>Diamond, Michael S.</creatorcontrib><creatorcontrib>Lavine, Kory J.</creatorcontrib><creatorcontrib>Rentschler, Stacey L.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JACC. Basic to translational science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brumback, Brittany D.</au><au>Dmytrenko, Oleksandr</au><au>Robinson, Ashley N.</au><au>Bailey, Adam L.</au><au>Ma, Pan</au><au>Liu, Jing</au><au>Hicks, Stephanie C.</au><au>Ng, Sherwin</au><au>Li, Gang</au><au>Zhang, David M.</au><au>Lipovsky, Catherine E.</au><au>Lin, Chieh-Yu</au><au>Diamond, Michael S.</au><au>Lavine, Kory J.</au><au>Rentschler, Stacey L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection</atitle><jtitle>JACC. Basic to translational science</jtitle><addtitle>JACC Basic Transl Sci</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>8</volume><issue>2</issue><spage>109</spage><epage>120</epage><pages>109-120</pages><issn>2452-302X</issn><eissn>2452-302X</eissn><abstract>[Display omitted]
•SARS-CoV-2 infects and replicates within cardiac pericytes in human organotypic cardiac slices.•SARS-CoV-2 infects human primary cardiac pericytes through an ACE2- and endosomal-dependent pathway.•Infection of human primary cardiac pericytes leads to up-regulation of inflammatory chemokine and cytokine expression, type I IFN signaling, mediators of vasoreactivity, and NF-κB–dependent cell death.•SARS-CoV-2 directly infects cardiac pericytes in patients with COVID-19 myocarditis.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36124009</pmid><doi>10.1016/j.jacbts.2022.09.001</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-1744-1238</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | cardiovascular disease COVID-19 Leading Edge Translational Research pericytes SARS-CoV-2 |
| title | Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection |
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