Serum Renin Levels Increase With Age in Boys Resulting in Higher Renin Levels in Young Men Compared to Young Women, and Soluble Angiotensin-Converting Enzyme 2 Correlates With Renin and Body Mass Index

Jehpsson, Lars; Sun, Jiangming; Nilsson, Peter M.; Edsfeldt, Andreas; Swärd, Per

doi:10.3389/fphys.2020.622179

Cited by 7 publications

(9 citation statements)

References 53 publications

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“…For example, based on the distributions of angiotensins we observed in this study, we calculated that we would have 80% power to detect differences in circulating ANG II and ANG-(1–7) between COVID-19-negative and COVID-19-positive hospitalized patients with ∼127 participants per group. In similar regard, we were underpowered to explore the relationship between other potential confounding covariates that may alter the RAS in patients with COVID-19, such as age, sex, body mass index (BMI), and corticosteroid use ( 19 – 21 ). For instance, dexamethasone, which is now a standard of care in severe COVID-19 has been shown to upregulate ACE and ACE2 ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

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Gibbs

Schaich

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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The renin-angiotensin system (RAS) is fundamental to COVID-19 pathobiology, due to the interaction between the SARS-CoV-2 virus and the angiotensin-converting enzyme-2 (ACE2) co-receptor for cellular entry. The prevailing hypothesis is that SARS-CoV-2-ACE2 interactions lead to an imbalance of the RAS, favoring pro-inflammatory Ang II related signaling at the expense of the anti-inflammatory Ang-(1-7) mediated alternative pathway. Indeed, multiple clinical trials targeting this pathway in COVID-19 are underway. Therefore, precise measurement of circulating RAS components is critical to understand the interplay of the RAS on COVID-19 outcomes. Multiple challenges exist in measuring the RAS in COVID-19 including improper patient controls, ex-vivo degradation and low concentrations of angiotensins, and unvalidated laboratory assays. Here, we conducted a prospective pilot study to enroll thirty-three moderate and severe COVID-19 patients and physiologically matched COVID-19 negative controls to quantify the circulating RAS. Our enrollment strategy led to physiologic matching of COVID-19 negative and positive moderate hypoxic respiratory failure cohorts, in contrast to the severe COVID-19 cohort which had increased severity of illness, prolonged ICU stay and increased mortality. Circulating Ang II and Ang-(1-7) levels were measured in the low picomolar (pM) range. We found no significant differences in circulating RAS peptides or peptidases between these three cohorts. The combined moderate and severe COVID-19 positive cohorts demonstrated a mild reduction in ACE activity compared to COVID-19 negative controls (2.2±0.9x105 vs. 2.9±0.8x105 RFU/mL, p=0.03). These methods may be useful in designing larger studies to physiologically match patients and quantify the RAS in COVID-19 RAS augmenting clinical trials.

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Section: Discussionmentioning

confidence: 99%

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

Files

Gibbs

Schaich

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Older age, male gender and higher BMI may enhance mACE2 shedding, leading to relative mACE2 deficiency. Jehpsson et al (116) reported that renin levels increase with age and from puberty, these levels are elevated among men than in women with a positive correlation with sACE2 levels. In circulation, renin levels and activities are correlated with AngII levels (117).…”

Section: Gendermentioning

confidence: 97%

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

et al. 2021

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The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.

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“…The tissue levels of mACE2 represent equilibrium between transcription/translation of mACE2 and shedding rate of sACE2. It was reported that a positive relationship exists between renin and sACE2 levels in male and female subjects, and between sACE2 levels and body mass index (BMI) in males, with possible implication for COVID-19 ( Jehpsson et al, 2021 ). Variations in mACE2 with age were first demonstrated using animal models ( Xie et al, 2006 ).…”

Section: The Human Ace2 Gene Variant Mrnasmentioning

confidence: 99%

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

Devaux

Camoin-Jau

2022

Front. Microbiol.

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It has been known for many years that the angiotensin-converting enzyme 2 (ACE2) is a cell surface enzyme involved in the regulation of blood pressure. More recently, it was proven that the severe acute respiratory syndrome coronavirus (SARS-CoV-2) interacts with ACE2 to enter susceptible human cells. This functional duality of ACE2 tends to explain why this molecule plays such an important role in the clinical manifestations of coronavirus disease 2019 (COVID-19). At the very start of the pandemic, a publication from our Institute (entitled “ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome”), was one of the first reviews linking COVID-19 to the duplicitous nature of ACE2. However, even given that COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin system (RAS), we were still far from understanding the complexity of the mechanisms which are controlled by ACE2 in different cell types. To gain insight into the physiopathology of SARS-CoV-2 infection, it is essential to consider the polymorphism and expression levels of the ACE2 gene (including its alternative isoforms). Over the past 2 years, an impressive amount of new results have come to shed light on the role of ACE2 in the pathophysiology of COVID-19, requiring us to update our analysis. Genetic linkage studies have been reported that highlight a relationship between ACE2 genetic variants and the risk of developing hypertension. Currently, many research efforts are being undertaken to understand the links between ACE2 polymorphism and the severity of COVID-19. In this review, we update the state of knowledge on the polymorphism of ACE2 and its consequences on the susceptibility of individuals to SARS-CoV-2. We also discuss the link between the increase of angiotensin II levels among SARS-CoV-2-infected patients and the development of a cytokine storm associated microvascular injury and obstructive thrombo-inflammatory syndrome, which represent the primary causes of severe forms of COVID-19 and lethality. Finally, we summarize the therapeutic strategies aimed at preventing the severe forms of COVID-19 that target ACE2. Changing paradigms may help improve patients’ therapy.

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Serum Renin Levels Increase With Age in Boys Resulting in Higher Renin Levels in Young Men Compared to Young Women, and Soluble Angiotensin-Converting Enzyme 2 Correlates With Renin and Body Mass Index

Cited by 7 publications

References 53 publications

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

A pilot study to assess the circulating renin-angiotensin system in COVID-19 acute respiratory failure

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

An update on angiotensin-converting enzyme 2 structure/functions, polymorphism, and duplicitous nature in the pathophysiology of coronavirus disease 2019: Implications for vascular and coagulation disease associated with severe acute respiratory syndrome coronavirus infection

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