Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes

Loganathan, Sundareswaran; Maheshkumar, K; Wankhar, Wankupar; Gurugubelli, Krishna Rao; Mahadevappa, Vidyashree Hodagatta; Lepcha, Lhakit; Choudhary, Arbind Kumar

doi:10.1016/j.resp.2020.103548

Cited by 90 publications

(84 citation statements)

References 157 publications

(249 reference statements)

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“…Furthermore, increased expression of ACE2 is also observed in cholangiocytes (59.7% of cells) and to a lesser extent in hepatocytes (2.6% of cells). This proves that SARS-CoV-2 infection impairs liver function by direct cytotoxicity due to the continuous replication of the virus in the above-mentioned cell populations[ 21 , 22 ]. Additionally, gene expression of ACE2 transmembrane serine protease 2 together with paired basic amino acid cleaving enzyme have also been proved in cholangiocytes and hepatocytes.…”

Section: Mechanisms Of Liver Injury In Covid-19 – When Can We Suspectmentioning

confidence: 92%

Liver injury in the era of COVID-19

Cichoż‐Lach

Michalak

2021

WJG

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.

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Section: Mechanisms Of Liver Injury In Covid-19 – When Can We Suspectmentioning

confidence: 92%

Liver injury in the era of COVID-19

Cichoż‐Lach

Michalak

2021

WJG

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“…Our bioinformatics analysis found ACE2 was significantly down-regulated in SARS-CoV-2 infected CMs, which was consistent with the prior reports of examining SARS-CoV-2 infected myocardium [ 50 ]. SARS-CoV-2 mediated myocardial apoptosis, cardiogenic shock, myocardial ischemia and inflammatory injury were related to the down-regulation of ACE2 in the myocardium [ [51] , [52] ]. The spike protein of SARS-CoV-2 might bind to TLR4 to trigger transmembrane stimulation [ [53] , [54] ].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction

Zhang

Zhu

et al. 2021

Computers in Biology and Medicine

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Background Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 20%–30% of patients hospitalized with COVID-19 have evidence of cardiac dysfunction. Xuebijing injection is a compound injection containing five traditional Chinese medicine ingredients, which can protect cells from SARS-CoV-2-induced cell death and improve cardiac function. However, the specific protective mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction remains unclear. Methods The therapeutic effect of Xuebijing injection on COVID-19 was validated by the TCM Anti COVID-19 (TCMATCOV) platform. RNA-sequencing (RNA-seq) data from GSE150392 was used to find differentially expressed genes (DEGs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. Data from GSE151879 was used to verify the expression of Angiotensin I Converting Enzyme 2 (ACE2) and central hub genes in both human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) and adult human CMs with SARS-CoV-2 infection. Results A total of 97 proteins were identified as the therapeutic targets of Xuebijing injection for COVID-19. There were 22 DEGs in SARS-CoV-2 infected hiPSC-CMs overlapped with the 97 therapeutic targets, which might be the therapeutic targets of Xuebijing injection on COVID-19-induced cardiac dysfunction. Based on the bioinformatics analysis, 7 genes (CCL2, CXCL8, FOS, IFNB1, IL-1A, IL-1B, SERPINE1) were identified as central hub genes and enriched in pathways including cytokines, inflammation, cell senescence and oxidative stress. ACE2, the receptor of SARS-CoV-2, and the 7 central hub genes were differentially expressed in at least two kinds of SARS-CoV-2 infected CMs. Besides, FOS and quercetin exhibited the tightest binding by molecular docking analysis. Conclusion Our study indicated the underlying protective effect of Xuebijing injection on COVID-19, especially on COVID19-induced cardiac dysfunction, which provided the theoretical basis for exploring the potential protective mechanism of Xuebijing injection on COVID19-induced cardiac dysfunction.

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“…This progression may be aggravated by cytokine storm with extensive release of proinflammatory cytokines from the deregulated immune system. 18 …”

Section: Discussionmentioning

confidence: 99%

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19

et al. 2021

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Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes

Cited by 90 publications

References 157 publications

Liver injury in the era of COVID-19

Liver injury in the era of COVID-19

Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19

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