scholarly journals Lack of association between genetic variants at ACE2 and TMPRSS2 genes involved in SARS-CoV-2 infection and human quantitative phenotypes

2020 ◽  
Author(s):  
Esteban Lopera ◽  
Adriaan van der Graaf ◽  
Pauline Lanting ◽  
Marije van der Geest ◽  
Jingyuan Fu ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Virus Clearance ◽  
Receptor Blockers ◽  
Males And Females ◽  
Metabolic Biomarkers ◽  
Larger Sample ◽  
Human Receptor

AbstractCoronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptomes, to flu-like symptoms, and in more severe cases, to pneumonia, acute respiratory distress syndrome and even death. Large differences in outcome have also been observed between males and females. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection uses the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual’s genetic predisposition to infection and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as 58 medications in 36,339 volunteers from the Lifelines population biobank, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed a suggestive association of polymorphisms within the ACE2 gene with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p=5.7×10−4), an association that is significantly stronger in females (pdiff=0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p=5.5×10−4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants play a role in diseases such as hypertension and chronic inflammation that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.

scholarly journals COVID-19 and Stroke Risk: A Double Whammy

2020 ◽  
Vol 56 (02) ◽  
pp. 058-061
Author(s):  
Alvee Saluja ◽  
Rajinder K. Dhamija
Keyword(s):  
Respiratory Symptoms ◽  
Stroke Risk ◽  
Angiotensin Ii Receptor ◽  
Tertiary Referral ◽  
Travel History ◽  
Stroke Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Receptor Blockers ◽  
Acute Stroke Treatment

AbstractThe emphasis so far during the COVID-19 pandemic has been on the respiratory manifestations with little attention being given to neurological manifestations. Literature has shown multiple cases of stroke being associated with COVID-19. Thus, there is great interest in the role of the virus in stroke pathogenesis. Regarding hyperacute and acute stroke treatment, the routine guidelines for thrombolysis and thrombectomy are to be followed with emphasis on high suspicion of COVID-19 in stroke cases with respiratory symptoms or with contact/travel history. Secondary risk factor treatment for hypertension, diabetes, dyslipidemia is a must. We recommend continuing angiotensin converting enzyme 2 inhibitors/angiotensin II receptor blockers (ARBs) in those who are taking these medications as per evidence available. Mandatory lockdown has led to delay in presentation to the hospital with a decrease in thrombolysis due to ineligibility and a corresponding increase in primary thrombectomies being performed. Telemedicine could be an important tool to triage cases worthy of tertiary referral from other strokes and must be encouraged.

scholarly journals Local Angiotensin-Converting Enzyme 2 Gene Expression in Kidney Allografts Is Not Affected by Renin-Angiotensin-Aldosterone Inhibitors

2021 ◽  
Vol 46 (2) ◽  
pp. 245-249
Author(s):  
Monika Cahova ◽  
Martin Kveton ◽  
Vojtech Petr ◽  
David Funda ◽  
Helena Dankova ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Kidney Transplant ◽  
Converting Enzyme ◽  
Transplant Recipients ◽  
Angiotensin Ii Receptor ◽  
Kidney Transplant Recipients ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers

<b><i>Background:</i></b> Preclinical studies suggested that pharmacological inhibition of the renin-angiotensin-aldosterone system (RAAS) by ACE inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) may increase local angiotensin-converting enzyme 2 (<i>ACE2</i>) expression. <b><i>Methods:</i></b> In this study, we evaluated the effect of ACEi or ARB treatment on expression of <i>ACE2</i>, <i>ACE</i>, and <i>AGTR1</i> in 3-month protocol kidney allograft biopsies of stable patients using RT-qPCR (<i>n</i> = 48). Protein ACE2 expression was assessed using immunohistochemistry from paraffin sections. <b><i>Results:</i></b> The therapy with RAAS blockers was not associated with increased <i>ACE2, ACE</i>, or <i>ATGR1</i> expression in kidney allografts and also ACE2 protein immunohistochemistry did not reveal differences among groups. <b><i>Conclusions:</i></b> ACEis or ARBs in kidney transplant recipients do not affect local ACE2 expression. This observation supports long-term RAAS treatment in kidney transplant recipients, despite acute complications such as COVID-19 where ACE2 serves as the entry protein for infection.

scholarly journals Renin Angiotensin Aldosterone System Antagonism in 2019 Novel Coronavirus Acute Lung Injury

2021 ◽  
Author(s):  
Davide Ventura ◽  
Amy L Carr ◽  
R Duane Davis ◽  
Scott Silvestry ◽  
Linda Bogar ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Ii Receptor ◽  
Pulmonary Tissue ◽  
Renin Angiotensin Aldosterone System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Membrane Bound ◽  
Raas Inhibitors ◽  
Novel Coronavirus

Abstract It has been established SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), a membrane-bound regulatory peptide, for host cell entry. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to increase ACE2 in type 2 pneumocytes pulmonary tissue. Controversy exists for the continuation of ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) in the current pandemic. ACE2 serves as regulatory enzyme in maintaining homeostasis between proinflammatory Angiotensin II and anti-inflammatory Angiotensin 1,7 peptides. Derangements in these peptides are associated with cardiovascular disease and are implicated in the progression of acute respiratory distress syndrome (ARDS). Augmentation of the ACE2/Ang1,7 axis represent a critical target in the supportive management of COVID-19 associated lung disease. Observational data describing the use of RAAS inhibitors in the setting of SARS-CoV-2 have not borne signals of harm to date. However, equipoise persists requiring an analysis of novel agents including recombinant human-ACE2 and existing RAAS inhibitors while balancing ongoing controversies associated with increased coronavirus infectivity and virulence.

scholarly journals Sport Participation Influences Perceptions of Mate Characteristics

2012 ◽  
Vol 10 (1) ◽  
pp. 147470491201000 ◽  
Author(s):  
Albrecht I. Schulte-Hostedde ◽  
Mark A. Eys ◽  
Michael Emond ◽  
Michael Buzdon
Keyword(s):  
Mate Choice ◽  
Sport Participation ◽  
Team Sport ◽  
Male Athletes ◽  
Future Studies ◽  
The Social ◽  
Initial Hypothesis ◽  
Males And Females ◽  
Larger Sample

Sport provides a context in which mate choice can be facilitated by the display of athletic prowess. Previous work has shown that, for females, team sport athletes are more desirable as mates than individual sport athletes and non-participants. In the present study, the perceptions of males and females were examined regarding potential mates based on sport participation. It was predicted that team sport athletes would be more positively perceived than individual sport athletes and non-participants by both males and females. A questionnaire, a photograph, and manipulated descriptions were used to gauge perceptual differences with respect to team sport athletes, individual sport athletes, and extracurricular club participants for 125 females and 119 males from a Canadian university. Both team and individual sport athletes were perceived as being less lazy, more competitive, and healthier than non-participants by both males and females. Interestingly, females perceived male athletes as more promiscuous than non-athletes, which upholds predictions based on previous research indicating (a) athletes have more sexual partners than non-athletes, and (b) females find athletes more desirable as partners than non-participants. Surprisingly, only males perceived female team sport athletes as more dependable than non-participants, and both team and individual sport athletes as more ambitious. This raises questions regarding the initial hypothesis that male team athletes would be perceived positively by females because of qualities such as the ability to cooperate, likeability, and the acceptance of responsibilities necessary for group functioning. Future studies should examine similar questions with a larger sample size that encompasses multiple contexts, taking into account the role of the social profile of sport in relation to mate choice and perception.

scholarly journals Atrial fibrillation and arterial hypertension

2011 ◽  
Vol 17 (4) ◽  
pp. 293-304
Author(s):  
E. I. Baranova
Keyword(s):  
Atrial Fibrillation ◽  
Arterial Hypertension ◽  
Enzyme Inhibitors ◽  
Anticoagulation Therapy ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Angiotensin Ii Receptor ◽  
Primary And Secondary Prevention ◽  
Converting Enzyme Inhibitors ◽  
Receptor Blockers

Review deals with atrial fibrillation and arterial hypertension. Possible pathological mechanisms of atrial fibrillation due to hypertension include haemodynamic effects, structural and electrophysiological heart remodeling partly connected with activation of renin-angiotensin-aldosterone system. Problems of primary and secondary prevention of atrial fibrillation in hypertensive patients are discussed, particularly the role of antihypertensive treatment including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Risk stratification for stroke and thromboembolism and anticoagulation therapy are discussed.

scholarly journals Atrial fibrillation and arterial hypertension

2011 ◽  
Vol 17 (4) ◽  
pp. 293-304 ◽  
Author(s):  
E. I. Baranova
Keyword(s):  
Atrial Fibrillation ◽  
Arterial Hypertension ◽  
Enzyme Inhibitors ◽  
Anticoagulation Therapy ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Angiotensin Ii Receptor ◽  
Primary And Secondary Prevention ◽  
Converting Enzyme Inhibitors ◽  
Receptor Blockers

Review deals with atrial fibrillation and arterial hypertension. Possible pathological mechanisms of atrial fibrillation due to hypertension include haemodynamic effects, structural and electrophysiological heart remodeling partly connected with activation of renin-angiotensin-aldosterone system. Problems of primary and secondary prevention of atrial fibrillation in hypertensive patients are discussed, particularly the role of antihypertensive treatment including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Risk stratification for stroke and thromboembolism and anticoagulation therapy are discussed.

Twenty years of progress in angiotensin converting enzyme 2 and its link to SARS-CoV-2 disease

2020 ◽  
Vol 134 (19) ◽  
pp. 2645-2664 ◽  
Author(s):  
Carlos M. Ferrario ◽  
Sarfaraz Ahmad ◽  
Leanne Groban
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Human Subjects ◽  
Adverse Outcomes ◽  
Converting Enzyme ◽  
Disease Evolution ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity Binding Site ◽  
Receptor Blockers

Abstract The virulence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the aggressive nature of the disease has transformed the universal pace of research in the desperate attempt to seek effective therapies to halt the morbidity and mortality of this pandemic. The rapid sequencing of the SARS-CoV-2 virus facilitated identification of the receptor for angiotensin converting enzyme 2 (ACE2) as the high affinity binding site that allows virus endocytosis. Parallel evidence that coronavirus disease 2019 (COVID-19) disease evolution shows greater lethality in patients with antecedent cardiovascular disease, diabetes, or even obesity questioned the potential unfavorable contribution of angiotensin converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers as facilitators of adverse outcomes due to the ability of these therapies to augment the transcription of Ace2 with consequent increase in protein formation and enzymatic activity. We review, here, the specific studies that support a role of these agents in altering the expression and activity of ACE2 and underscore that the robustness of the experimental data is associated with weak clinical long-term studies of the existence of a similar regulation of tissue or plasma ACE2 in human subjects.

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