Targeting Angiotensin-Converting Enzyme-2/Angiotensin-(1-7)/Mas Receptor Axis in the Vascular Progenitor Cells for Cardiovascular Diseases

Jarajapu, Yagna

doi:10.1124/mol.119.117580

Cited by 20 publications

(21 citation statements)

References 138 publications

(130 reference statements)

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“…It has already been demonstrated that hyperactivation of AT 1 R by Ang II may lead to excessive activation of the Nlrp3 inflammasome and cell death by pyroptosis in lung epithelium cells, endothelium, and cardiomyocytes [11][12][13][14]. By contrast, after binding to MasR, Ang (1-7) displays the opposite effect and has been demonstrated to stimulate proliferation of skeletal muscle and hematopoietic cells [6,15]. Unfortunately, because of ACE2 internalization during SARS-CoV-2 infection Ang II is not processed to Ang (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

Ratajczak

Bujko

Ciechanowicz

et al. 2020

Stem Cell Rev and Rep

142

144

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Angiotensin-converting enzyme 2 (ACE2) plays an important role as a member of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II (Ang II) into angiotensin (1-7) (Ang [1-7]). But at the same time, while expressed on the surface of human cells, ACE2 is the entry receptor for SARS-CoV-2. Expression of this receptor has been described in several types of cells, including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which raises a concern that the virus may infect and damage the stem cell compartment. We demonstrate for the first time that ACE2 and the entry-facilitating transmembrane protease TMPRSS2 are expressed on very small CD133 + CD34 + Lin − CD45 − cells in human umbilical cord blood (UCB), which can be specified into functional HSCs and EPCs. The existence of these cells known as very small embryonic-like stem cells (VSELs) has been confirmed by several laboratories, and some of them may correspond to putative postnatal hemangioblasts. Moreover, we demonstrate for the first time that, in human VSELs and HSCs, the interaction of the ACE2 receptor with the SARS-CoV-2 spike protein activates the Nlrp3 inflammasome, which if hyperactivated may lead to cell death by pyroptosis. Based on this finding, there is a possibility that human VSELs residing in adult tissues could be damaged by SARS-CoV-2, with remote effects on tissue/organ regeneration. We also report that ACE2 is expressed on the surface of murine bone marrow-derived VSELs and HSCs, although it is known that murine cells are not infected by SARS-CoV-2. Finally, human and murine VSELs express several RAAS genes, which sheds new light on the role of these genes in the specification of early-development stem cells.

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Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

Ratajczak

Bujko

Ciechanowicz

et al. 2020

Stem Cell Rev and Rep

142

144

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“…ACE2 is widely expressed in human tissues, including alveloar type 2 (AT2), capillary epithelium, the heart, liver, kidney, and endothelial cells [5]. ACE2 is also expressed in hematopoietic stem and progenitor cells [6]. ACE2 stimulates mobilization of progenitor cells from bone marrow, migration to areas of vascular damage and revascularization of ischemic areas in pathological conditions like hypoxic exercise [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…ACE2 is also expressed in hematopoietic stem and progenitor cells [6]. ACE2 stimulates mobilization of progenitor cells from bone marrow, migration to areas of vascular damage and revascularization of ischemic areas in pathological conditions like hypoxic exercise [6][7][8]. SARS-CoV-2 also probably invades host cells via CD147 (also known as Basigin or EMMPRIN) [9].…”

Section: Introductionmentioning

confidence: 99%

Is COVID-19 a New Hematologic Disease?

Debuc

Smadja

2020

Stem Cell Rev and Rep

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SARS-CoV-2 viruses are positive single-stranded RNA viruses, whose infection can be asymptomatic or lead to the coronavirus disease 2019 . Covid-19 is a respiratory infection with a significant impact on the hematopoietic system and hemostasis leading to several cardiovascular complications. Hematologic consequences of this new infection allowed medical community to start new treatment approaches concerning infection going from targeted anti-inflammatory drugs to anticoagulation or stem cell therapies. A better understanding of Covid-19 pathophysiology, in particular hematological disorders, will help to choose appropriate treatment strategies.

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“…Also, viral RNA could be isolated in plasma or serum from COVID-19 asymptomatic patients in a very low concentration [4]. It has been reported that ACE2, which has been described as the main receptor for SARS-CoV-2, is expressed in hematopoietic stem and progenitor cells especially under hypoxia situations [8]. In 2004 it was found that lymphocytes have higher concentration of SARS-CoV than plasma and that it can replicate inside them [4].…”

Section: Discussionmentioning

confidence: 99%

No transmission of SARS-CoV-2 in a patient undergoing allogeneic hematopoietic cell transplantation from a matched-related donor with unknown COVID-19

Campo

Arias

Lopez

et al. 2020

Transfusion and Apheresis Science

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Targeting Angiotensin-Converting Enzyme-2/Angiotensin-(1-7)/Mas Receptor Axis in the Vascular Progenitor Cells for Cardiovascular Diseases

Cited by 20 publications

References 138 publications

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome

Is COVID-19 a New Hematologic Disease?

No transmission of SARS-CoV-2 in a patient undergoing allogeneic hematopoietic cell transplantation from a matched-related donor with unknown COVID-19

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