Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 – implications for microvascular inflammation and hypercoagulopathy in COVID-19

He, Liqun; Mäe, Maarja Andaloussi; Muhl, Lars; Sun, Ying; Pietilä, Riikka; Nahar, Khayrun; Liébanas, Elisa Vázquez; Fagerlund, Malin Jonsson; Oldner, Anders; Liu, Jianping; Genové, Guillem; Zhang, Lei; Xie, Yuan; Leptidis, Stefanos; Mocci, Giuseppe; Stritt, Simon; Osman, Ahmed; Anisimov, Andrey; Hemanthakumar, Karthik Amudhala; Räsänen, Markus; Mirabeau, Olivier; Hansson, Emil M.; Björkegren, Johan; Vanlandewijck, Michael; Blomgren, Klas; Mäkinen, Taija; Peng, Xiaorong; Arnold, Thomas D.; Alitalo, Kari; Eriksson, Lars; Lendahl, Urban; Betsholtz, Christer

doi:10.1101/2020.05.11.088500

Cited by 122 publications

(172 citation statements)

References 93 publications

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…These data support our scRNA-seq analysis of the HPAP dataset which identified a subset of pericytes, marked by PDGFRB and COL1A1, that express moderate levels of ACE2 ( Figure 1B). In addition, our findings are supportive of recent reports of pericyte-specific vascular expression of ACE2 in brain and heart tissue (Chen et al, 2020;He, 2020). Importantly, the absence of TMPRSS2 co-expression makes it highly unlikely that islet pericytes are susceptible to direct SARS-CoV-2 infection.…”

Section: Ace2 Is Localized To Islet and Exocrine Tissue Capillariessupporting

confidence: 90%

SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Pancreas but are Not Enriched in Islet Endocrine Cells

Coate

Cha

Shrestha

et al. 2020

Preprint

View full text Add to dashboard Cite

Summary/AbstractReports of new-onset diabetes and diabetic ketoacidosis in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2, the virus that causes COVID-19, is directly cytotoxic to pancreatic islet β cells. This model would require binding and entry of SARS-CoV-2 into host cells via cell surface co-expression of ACE2 and TMPRSS2, the putative receptor and effector protease, respectively. To define ACE2 and TMPRSS2 expression in the human pancreas, we examined six transcriptional datasets from primary human islet cells and assessed protein expression by immunofluorescence in pancreata from donors with and without diabetes. ACE2 and TMPRSS2 transcripts were low or undetectable in pancreatic islet endocrine cells as determined by bulk or single cell RNA sequencing, and neither protein was detected in α or β cells from any of these donors. Instead, ACE2 protein was expressed in the islet and exocrine tissue microvasculature and also found in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. The absence of ACE2 and TMPRSS2 co-expression in islet endocrine cells makes it unlikely that SARS-CoV-2 directly affects pancreatic islet β cells.

show abstract

Section: Ace2 Is Localized To Islet and Exocrine Tissue Capillariessupporting

confidence: 90%

SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Pancreas but are Not Enriched in Islet Endocrine Cells

Coate

Cha

Shrestha

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Cardot-Leccia et al (96) reported wall thickening of the venules and alveolar capillaries in lung tissue of a deceased COVID-19 patient, accompanied by a marked decrease in pericytes, compared to normal lung parenchyma. Combined with the findings of He et al (95) and the highly infectious potential of pericytes demonstrated by single cell RNA sequencing studies (28), these data seem to support a potential "pericyte hypothesis" as a mechanism for microvascular dysfunction in the pathogenesis of COVID-19. Moreover, infection and loss of pericytes would result in a dysregulation of the cross-talk between pericytes and endothelial cells, promoting capillary endothelial dysfunction, which would explain the wall thickening of venules and capillaries observed in the data from Cardot-Leccia et al (96).…”

Section: Cellular Cross-talk: Endothelial Cells and Pericytesmentioning

confidence: 53%

“…A balance between ANGPTs and TIE2 is key for the maintenance of endothelial stability and vascular integrity (28, 94); therefore, it is possible that a breakdown of the cross-talk between pericytes and endothelial cells disrupts this balance and results in a compromised vasculature that is prone to a pro-inflammatory, pro-coagulant state. Whilst these findings were observed in normal heart tissue, this is supported by a pericyte-specific infection by SARS-CoV-2 in experimental (95) and human histological studies (96).…”

Section: Cellular Cross-talk: Endothelial Cells and Pericytesmentioning

confidence: 79%

Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction

Roberts

Colley

Agbaedeng

et al. 2020

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

The coronavirus pandemic has reportedly infected over 31.5 million individuals and caused over 970,000 deaths worldwide (as of 22nd Sept 2020). This novel coronavirus, officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although primarily causes significant respiratory distress, can have significant deleterious effects on the cardiovascular system. Severe cases of the virus frequently result in respiratory distress requiring mechanical ventilation, often seen, but not confined to, individuals with pre-existing hypertension and cardiovascular disease, potentially due to the fact that the virus can enter the circulation via the lung alveoli. Here the virus can directly infect vascular tissues, via TMPRSS2 spike glycoprotein priming, thereby facilitating ACE-2-mediated viral entry. Clinical manifestations, such as vasculitis, have been detected in a number of vascular beds (e.g., lungs, heart, and kidneys), with thromboembolism being observed in patients suffering from severe coronavirus disease (COVID-19), suggesting the virus perturbs the vasculature, leading to vascular dysfunction. Activation of endothelial cells via the immune-mediated inflammatory response and viral infection of either endothelial cells or cells involved in endothelial homeostasis, are some of the multifaceted mechanisms potentially involved in the pathogenesis of vascular dysfunction within COVID-19 patients. In this review, we examine the evidence of vascular manifestations of SARS-CoV-2, the potential mechanism(s) of entry into vascular tissue and the contribution of endothelial cell dysfunction and cellular crosstalk in this vascular tropism of SARS-CoV-2. Moreover, we discuss the current evidence on hypercoagulability and how it relates to increased microvascular thromboembolic complications in COVID-19.

show abstract

“…High expression of ACE2 is observed in pericytes. Pericytes are located outside endothelial cell of capillary and part of venules which might indicate for SARS-CoV-2 infection of pericytes leading to increased thrombogenicity, and hypercoagulation seen in COVID-19 patients and a higher probability for acute coronary syndromes (ACS) 67,68 .…”

Section: Covid-19 and Heart Diseasesmentioning

confidence: 99%

COVID-19 and the World with Co-Morbidities of Heart Disease, Hypertension and Diabetes

Anand¹,

Sangeetha²,

Fathah³

et al. 2020

J Pure Appl Microbiol

View full text Add to dashboard Cite

Newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) pandemic has now spread across the globe in past few months while affecting 26 million people and leading to more than 0.85 million deaths as on 2nd September, 2020. Severity of SARS-CoV-2 infection increases in COVID-19 patients due to pre-existing health co-morbidities. This mini-review has focused on the three significant co-morbidities viz., heart disease, hypertension, and diabetes, which are posing high health concerns and increased mortality during this ongoing pandemic. The observed co-morbidities have been found to be associated with the increasing risk factors for SARS-CoV-2 infection and COVID-19 critical illness as well as to be associated positively with the worsening of the health condition of COVID-19 suffering individuals resulting in the high risk for mortality. SARS-CoV-2 enters host cell via angiotensin-converting enzyme 2 receptors. Regulation of crucial cardiovascular functions and metabolisms like blood pressure and sugar levels are being carried out by ACE2. This might be one of the reasons that contribute to the higher mortality in COVID-19 patients having co-morbidities. Clinical investigations have identified higher levels of creatinine, cardiac troponin I, alanine aminotransferase, NT-proBNP, creatine kinase, D-dimer, aspartate aminotransferase and lactate dehydrogenase in patients who have succumbed to death from COVID-19 as compared to recovered individuals. More investigations are required to identify the modes behind increased mortality in COVID-19 patients having co-morbidities of heart disease, hypertension, and diabetes. This will enable us to design and develop suitable therapeutic strategies for reducing the mortality. More attention and critical care need to be paid to such high risk patients suffering from co-morbidities during COVID-19 pandemic.

show abstract

Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 – implications for microvascular inflammation and hypercoagulopathy in COVID-19

Cited by 122 publications

References 93 publications

SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Pancreas but are Not Enriched in Islet Endocrine Cells

SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Pancreas but are Not Enriched in Islet Endocrine Cells

Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction

COVID-19 and the World with Co-Morbidities of Heart Disease, Hypertension and Diabetes

Contact Info

Product

Resources

About