SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril
Copyright © 2023 Elsevier B.V. All rights reserved..
Although the clinical manifestation of COVID-19 is mainly respiratory symptoms, approximately 20% of patients suffer from cardiac complications. COVID-19 patients with cardiovascular disease have higher severity of myocardial injury and poor outcomes. The underlying mechanism of myocardial injury caused by SARS-CoV-2 infection remains unclear. Using a non-transgenic mouse model infected with Beta variant (B.1.351), we found that the viral RNA could be detected in lungs and hearts of infected mice. Pathological analysis showed thinner ventricular wall, disorganized and ruptured myocardial fiber, mild inflammatory infiltration, and mild epicardia or interstitial fibrosis in hearts of infected mice. We also found that SARS-CoV-2 could infect cardiomyocytes and produce infectious progeny viruses in human pluripotent stem cell-derived cardiomyocyte-like cells (hPSC-CMs). SARS-CoV-2 infection caused apoptosis, reduction of mitochondrial integrity and quantity, and cessation of beating in hPSC-CMs. In order to dissect the mechanism of myocardial injury caused by SARS-CoV-2 infection, we employed transcriptome sequencing of hPSC-CMs at different time points after viral infection. Transcriptome analysis showed robust induction of inflammatory cytokines and chemokines, up-regulation of MHC class I molecules, activation of apoptosis signaling and cell cycle arresting. These may cause aggravate inflammation, immune cell infiltration, and cell death. Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:215 |
---|---|
Enthalten in: |
Antiviral research - 215(2023) vom: 01. Juli, Seite 105636 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Huang, Xiaohan [VerfasserIn] |
---|
Links: |
---|
Themen: |
9G64RSX1XD |
---|
Anmerkungen: |
Date Completed 05.06.2023 Date Revised 12.06.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.antiviral.2023.105636 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM357103335 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM357103335 | ||
003 | DE-627 | ||
005 | 20231226071853.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.antiviral.2023.105636 |2 doi | |
028 | 5 | 2 | |a pubmed24n1190.xml |
035 | |a (DE-627)NLM357103335 | ||
035 | |a (NLM)37207821 | ||
035 | |a (PII)S0166-3542(23)00114-6 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Huang, Xiaohan |e verfasserin |4 aut | |
245 | 1 | 0 | |a SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 05.06.2023 | ||
500 | |a Date Revised 12.06.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
520 | |a Although the clinical manifestation of COVID-19 is mainly respiratory symptoms, approximately 20% of patients suffer from cardiac complications. COVID-19 patients with cardiovascular disease have higher severity of myocardial injury and poor outcomes. The underlying mechanism of myocardial injury caused by SARS-CoV-2 infection remains unclear. Using a non-transgenic mouse model infected with Beta variant (B.1.351), we found that the viral RNA could be detected in lungs and hearts of infected mice. Pathological analysis showed thinner ventricular wall, disorganized and ruptured myocardial fiber, mild inflammatory infiltration, and mild epicardia or interstitial fibrosis in hearts of infected mice. We also found that SARS-CoV-2 could infect cardiomyocytes and produce infectious progeny viruses in human pluripotent stem cell-derived cardiomyocyte-like cells (hPSC-CMs). SARS-CoV-2 infection caused apoptosis, reduction of mitochondrial integrity and quantity, and cessation of beating in hPSC-CMs. In order to dissect the mechanism of myocardial injury caused by SARS-CoV-2 infection, we employed transcriptome sequencing of hPSC-CMs at different time points after viral infection. Transcriptome analysis showed robust induction of inflammatory cytokines and chemokines, up-regulation of MHC class I molecules, activation of apoptosis signaling and cell cycle arresting. These may cause aggravate inflammation, immune cell infiltration, and cell death. Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Apoptosis | |
650 | 4 | |a Captopril | |
650 | 4 | |a Cardiomyocyte | |
650 | 4 | |a Inflammation | |
650 | 4 | |a SARS-CoV-2 | |
650 | 7 | |a Captopril |2 NLM | |
650 | 7 | |a 9G64RSX1XD |2 NLM | |
650 | 7 | |a Angiotensin-Converting Enzyme Inhibitors |2 NLM | |
700 | 1 | |a Fan, Wenxia |e verfasserin |4 aut | |
700 | 1 | |a Sun, Jing |e verfasserin |4 aut | |
700 | 1 | |a Yang, Jiaqing |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Yanjun |e verfasserin |4 aut | |
700 | 1 | |a Wang, Qian |e verfasserin |4 aut | |
700 | 1 | |a Li, Pingchao |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Yudi |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Shengnan |e verfasserin |4 aut | |
700 | 1 | |a Li, Heying |e verfasserin |4 aut | |
700 | 1 | |a Wang, Jianhua |e verfasserin |4 aut | |
700 | 1 | |a Feng, Liqiang |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
700 | 1 | |a Chen, Ling |e verfasserin |4 aut | |
700 | 1 | |a Qu, Linbing |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Antiviral research |d 1983 |g 215(2023) vom: 01. Juli, Seite 105636 |w (DE-627)NLM012601756 |x 1872-9096 |7 nnns |
773 | 1 | 8 | |g volume:215 |g year:2023 |g day:01 |g month:07 |g pages:105636 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.antiviral.2023.105636 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 215 |j 2023 |b 01 |c 07 |h 105636 |