Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421

The molecular mechanisms controlling the expression of ACE2, a critical regulator of cardiovascular homoeostasis, remain poorly defined. In the present study, we show that miR-421 regulates expression of ACE2 in cardiac myofibroblasts, identifying a possible new therapeutic target in cardiovascular disease.

Download Full-text

Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target

Intensive Care Medicine ◽

10.1007/s00134-020-05985-9 ◽

2020 ◽

Vol 46 (4) ◽

pp. 586-590 ◽

Cited By ~ 671

Author(s):

Haibo Zhang ◽

Josef M. Penninger ◽

Yimin Li ◽

Nanshan Zhong ◽

Arthur S. Slutsky

Keyword(s):

Angiotensin Converting Enzyme ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Converting Enzyme ◽

Potential Therapeutic Target ◽

Angiotensin Converting Enzyme 2

Download Full-text

The regulation of ACE-2 in the heart and lungs

The Southwest Respiratory and Critical Care Chronicles ◽

10.12746/swrccc.v9i40.895 ◽

2021 ◽

Vol 9 (40) ◽

pp. 47-52

Author(s):

Jonathan Kopel ◽

Thomas Tenner ◽

Gregory Brower

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Cardiovascular Disease ◽

Angiotensin Converting Enzyme ◽

Molecular Mechanisms ◽

Physiological Responses ◽

Cardiovascular Complications ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Metabolism Regulation

The pathogenesis of SARS-CoV-2 infection or COVID-19 disease remains an active and rapidly evolving area of investigation. Currently, the angiotensin-converting enzyme 2 protein (ACE-2) is the primary receptor implicated in the pathogenesis of SARS-CoV-2. In normal physiological responses, the ACE-2 has important roles in regulating the renin-angiotensin systems (RAS) in several organs, including the heart, kidney, and lungs. Dysregulation of ACE-2 has been linked to heart failure, pulmonary hypertension, and diabetic cardiovascular complications. Two main risk factors for COVID-19 include hypertension and cardiovascular disease. However, the precise mechanism causing these risk factors for COVID-19 infectivity remains unknown. In this paper, we provide possible molecular mechanisms that underlie the cardiovascular risk factors for COVID-19. Keywords: SARS-CoV-2, COVID-19, angiotensin converting enzyme-2 (ACE-2), hormones, cardiovascular, hypoxia, metabolism, regulation, and pathophysiology

Download Full-text

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

10.26434/chemrxiv.12186624.v3 ◽

2020 ◽

Author(s):

Cristina Garcia-Iriepa ◽

Cecilia Hognon ◽

Antonio Francés-Monerris ◽

Isabel Iriepa ◽

Tom Miclot ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Molecular Mechanisms ◽

Molecular Design ◽

Binding Free Energy ◽

Transmembrane Protein ◽

Spike Protein ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Rational Molecular Design ◽

Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

Download Full-text

Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation

European Heart Journal ◽

10.1093/eurheartj/ehaa697 ◽

2020 ◽

Vol 41 (41) ◽

pp. 4037-4046 ◽

Cited By ~ 3

Author(s):

Lars Wallentin ◽

Johan Lindbäck ◽

Niclas Eriksson ◽

Ziad Hijazi ◽

John W Eikelboom ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiovascular Disease ◽

Angiotensin Converting Enzyme ◽

Association Studies ◽

Cell Surface Receptor ◽

Genome Wide Association Studies ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Cellular Expression ◽

Male Sex

Abstract Aims The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. Methods and results Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level. Conclusions Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.

Download Full-text

Targeting angiotensin-converting enzyme 2 as a new therapeutic target for cardiovascular diseases

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2013-0488 ◽

2014 ◽

Vol 92 (7) ◽

pp. 558-565 ◽

Cited By ~ 17

Author(s):

Nirmal Parajuli ◽

Tharmarajan Ramprasath ◽

Vaibhav B. Patel ◽

Wang Wang ◽

Brendan Putko ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Diseases ◽

Angiotensin Converting Enzyme ◽

Therapeutic Target ◽

Ang Ii ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Heart Failure Patients ◽

Positive Effects ◽

Mas Receptor

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes several vasoactive peptides, including angiotensin II (Ang-II; a vasoconstrictive/proliferative peptide), which it converts to Ang-(1–7). Ang-(1–7) acts through the Mas receptor to mediate vasodilatory/antiproliferative actions. The renin–angiotensin system involving the ACE–Ang-II–Ang-II type-1 receptor (AT1R) axis is antagonized by the ACE2–Ang-(1–7)–Mas receptor axis. Loss of ACE2 enhances adverse remodeling and susceptibility to pressure and volume overload. Human recombinant ACE2 may act to suppress myocardial hypertrophy, fibrosis, inflammation, and diastolic dysfunction in heart failure patients. The ACE2–Ang-(1–7)–Mas axis may present a new therapeutic target for the treatment of heart failure patients. This review is mainly focused on the analysis of ACE2, including its influence and potentially positive effects, as well as the potential use of human recombinant ACE2 as a novel therapy for the treatment cardiovascular diseases, such as hypertension and heart failure.

Download Full-text

Infection of Human Cells by SARS-CoV-2 and Molecular Overview of Gastrointestinal, Neurological, and Hepatic Problems in COVID-19 Patients

Journal of Clinical Medicine ◽

10.3390/jcm10214802 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4802

Author(s):

Mahdie Rahban ◽

Agata Stanek ◽

Amirreza Hooshmand ◽

Yasaman Khamineh ◽

Salma Ahi ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Angiotensin Converting Enzyme ◽

Intestinal Permeability ◽

Molecular Mechanisms ◽

External Environment ◽

Gastrointestinal Disorders ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Liver Infection

The gastrointestinal tract is the body’s largest interface between the host and the external environment. People infected with SARS-CoV-2 are at higher risk of microbiome alterations and severe diseases. Recent evidence has suggested that the pathophysiological and molecular mechanisms associated with gastrointestinal complicity in SARS-CoV-2 infection could be explained by the role of angiotensin-converting enzyme-2 (ACE2) cell receptors. These receptors are overexpressed in the gut lining, leading to a high intestinal permeability to foreign pathogens. It is believed that SARS-CoV-2 has a lesser likelihood of causing liver infection because of the diminished expression of ACE2 in liver cells. Interestingly, an interconnection between the lungs, brain, and gastrointestinal tract during severe COVID-19 has been mentioned. We hope that this review on the molecular mechanisms related to the gastrointestinal disorders as well as neurological and hepatic manifestations experienced by COVID-19 patients will help scientists to find a convenient solution for this and other pandemic events.

Download Full-text