scholarly journals Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?

2020 ◽  
Vol 8 (10) ◽  
pp. 1492
Author(s):  
Lorella Pascolo ◽  
Gabriella Zito ◽  
Luisa Zupin ◽  
Stefania Luppi ◽  
Elena Giolo ◽  
...  
Keyword(s):  
Male Fertility ◽  
Assisted Reproductive Technologies ◽  
Seminal Fluid ◽  
Sperm Quality ◽  
Renin Angiotensin System ◽  
Reproductive Technologies ◽  
Host Cells ◽  
Pharmacological Intervention ◽  
Angiotensin System ◽  
Renin Angiotensin

The current knowledge concerning the connection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the renin–angiotensin system (RAS) system in the male reproductive apparatus is still limited, so dedicated studies are urgently required. Concerns about the male fertility consequences of SARS-CoV-2 infection have started to emerge, since epidemiologic studies observed that this coronavirus affects male patients more frequently and with increased severity, possibly because of the hormone-regulated expression of angiotensin-converting enzyme 2 (ACE2) receptor. A disturbance in fertility is also expected based on studies of the previous SARS-CoV infection, which targets the same ACE2 receptor when entering the host cells. In addition, bioinformatics analyses reveal the abundant expression of ACE2 receptor in the male reproductive tissues, particularly in the testis. It has been proposed that pharmacological intervention favoring the angiotensin-(1–7)/ACE2/Mas receptor pathway and increasing ACE2 expression and activity could greatly prevent inflammatory lesions in this area. Finally, in laboratories performing assisted reproductive technologies it is recommended that more attention should be paid not only to sperm quality but also to safety aspects. Data about the potential infectivity of seminal fluid are in fact conflicting and do not exclude risks for both personnel and patients. The potential infectivity of SARS-CoV-2 in reproductive male tissues should be strongly considered and further investigated for the proper management of in vitro fertilization procedures.

scholarly journals Regulation of Male Fertility by the Renin-Angiotensin System

2020 ◽  
Vol 21 (21) ◽  
pp. 7943
Author(s):  
Marta Gianzo ◽  
Nerea Subirán
Keyword(s):  
Blood Pressure ◽  
Male Infertility ◽  
Male Fertility ◽  
Seminal Fluid ◽  
Renin Angiotensin System ◽  
Design Tools ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Plasma Electrolytes ◽  
Sperm Functions

The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1350-1367 ◽  
Author(s):  
Matthew A. Sparks ◽  
Andrew M. South ◽  
Andrew D. Badley ◽  
Carissa M. Baker-Smith ◽  
Daniel Batlle ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Experimental Models ◽  
Multiple Organ ◽  
Host Cells ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Organ Systems

The coronavirus disease 2019 (COVID-19) pandemic is associated with significant morbidity and mortality throughout the world, predominantly due to lung and cardiovascular injury. The virus responsible for COVID-19—severe acute respiratory syndrome coronavirus 2—gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1–7) to reduce inflammation and fibrosis and mitigate end organ damage. As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. We provide researchers with a framework of best practices in basic and clinical research to interrogate the RAS using appropriate methodology, especially those who are relatively new to the field. This is crucial, as there are many limitations inherent in investigating the RAS in experimental models and in humans. We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1–7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor). Our goal is to ensure appropriate research methodology for investigations of the RAS in patients with severe acute respiratory syndrome coronavirus 2 and COVID-19 to ensure optimal rigor and reproducibility and appropriate interpretation of results from these investigations.

scholarly journals Quantifying Renin-Angiotensin-System Alterations in COVID-19

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2755
Author(s):  
Fabrizio Pucci ◽  
Filippo Annoni ◽  
Robson Augusto Souza dos Santos ◽  
Fabio Silvio Taccone ◽  
Marianne Rooman
Keyword(s):  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Physiological Processes ◽  
Open Questions ◽  
Clinical Investigations ◽  
Conflicting Evidence

The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes, among which inflammation and blood pressure regulation. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, and therefore a lot of research has been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical investigations and experimental analyzes quantifying, e.g., the levels and activity of RAS components. We performed a comprehensive meta-analysis of these data in view of disentangling the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. We also review the effects of several RAS-targeting drugs and how they could potentially help restore the normal RAS functionality and minimize the COVID-19 severity. Finally, we discuss the conflicting evidence found in the literature and the open questions on RAS dysregulation in SARS-CoV-2 infection whose resolution would improve our understanding of COVID-19.

scholarly journals Quantifying renin-angiotensin-system alterations in COVID-19

2021 ◽  
Author(s):  
Fabrizio Pucci ◽  
Filippo Annoni ◽  
Robson Augusto Souza dos Santos ◽  
Fabio Silvio Taccone ◽  
Marianne Rooman
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Entry Point ◽  
Host Cells ◽  
Pivotal Role ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Physiological Processes

Abstract The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, so many studies have been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical and experimental analyzes, which, for example, quantify the levels and activity of RAS components, in order to disentangle the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. Finally, we discussed the effects of some RAS-targeting drugs, and how they could potentially contribute to restore the normal RAS functionality and minimize COVID-19 severity.

scholarly journals Cessation of Renin-Angiotensin System Antagonists During the SARS-CoV-2 Pandemic – Do We Have the Evidence?

2020 ◽  
Vol 5 (3) ◽  
pp. 105-109
Author(s):  
Emanuel Blîndu ◽  
Renata Gerculy ◽  
Diana Opincariu ◽  
Daniel Cernica ◽  
Imre Benedek
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blockers ◽  
Healthcare Providers ◽  
Age Groups ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Angiotensin System ◽  
Renin Angiotensin

AbstractThe aim of this review is to provide a short update on whether treatment with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) has beneficial or harmful effects in patients infected with SARS-CoV-2. Epidemiological studies have shown that SARS-CoV-2 infects all age groups, presenting a higher incidence in elderly patients with various comorbidities such as hypertension, diabetes mellitus, and cardiovascular diseases. A large proportion of these patients are treated with ACEIs and ARBs. Since it has been demonstrated that SARS-CoV-2 uses angiotensin converting enzyme type 2 (ACE2) as an entry point into host cells, it is important to know whether ACEIs and ARBs could modify the expression of this enzyme, and thus promote the viral infection. Animal studies and a few studies in humans have shown that renin angiotensin system (RAS) inhibitors increase tissue expression of ACE2, but with potentially beneficial effects. In this context, it is imperative to provide appropriate guidance for clinicians and patients. The major cardiology associations across the world have released statements in which they recommend healthcare providers and patients to continue their treatments for hyper-tension and heart failure as prescribed.

scholarly journals Renin–Angiotensin–Aldosterone System Inhibitors in Patients with COVID-19: General Considerations and Clinical Implications

2020 ◽  
Vol 33 (1) ◽  
pp. 1-5
Author(s):  
Neiberg de Alcantara Lima ◽  
Pedro Yuri Paiva Lima ◽  
Ricardo Lessa de Castro Junior ◽  
Eric Martin Sieloff ◽  
Stela Maria Vitorino Sampaio
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Viral Transmission ◽  
Host Cells ◽  
Angiotensin Receptors ◽  
Clinical Implications ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Initially reported in China at the end of 2019, the coronavirus pandemic has now reached an international scale with more than 1.5 million cases worldwide and more than eighty thousands deaths by April 8th of this year. Recent studies have shown that the virus invades host cells by the angiotensin-converting enzyme 2 receptor, making it essential to viral transmission. Concerns have been raised about possible benefits and harms associated with the use of ACE inhibitors and angiotensin receptors blockers in these patients. However, there is lack of evidence to recommend even temporarily discontinuing renin-angiotensin system inhibitors/blockers in patients infected with the SARS-CoV-2.

scholarly journals COVID-19, Renin-Angiotensin System and Endothelial Dysfunction

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1652 ◽  
Author(s):  
Razie Amraei ◽  
Nader Rahimi
Keyword(s):  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Renin Angiotensin System ◽  
Vascular Damage ◽  
Host Cells ◽  
Ras Signaling ◽  
Global Public Health ◽  
Angiotensin System ◽  
Renin Angiotensin

The newly emergent novel coronavirus disease 2019 (COVID-19) outbreak, which is caused by SARS-CoV-2 virus, has posed a serious threat to global public health and caused worldwide social and economic breakdown. Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1–9 and Ang 1–7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. Once inside the host cells, SARS-CoV-2 induces acute respiratory distress syndrome (ARDS), stimulates immune response (i.e., cytokine storm) and vascular damage. SARS-CoV-2 induced endothelial cell injury could exacerbate endothelial dysfunction, which is a hallmark of aging, hypertension, and obesity, leading to further complications. The pathophysiology of endothelial dysfunction and injury offers insights into COVID-19 associated mortality. Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality. We also surveyed the roles of cell adhesion molecules (CAMs), including CD209L/L-SIGN and CD209/DC-SIGN in SARS-CoV-2 infection and other related viruses. Understanding the molecular mechanisms of infection, the vascular damage caused by SARS-CoV-2 and pathways involved in the regulation of endothelial dysfunction could lead to new therapeutic strategies against COVID-19.

scholarly journals ACE2 (Angiotensin-Converting Enzyme 2) in Cardiopulmonary Diseases

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 651-661 ◽  
Author(s):  
Ravindra K. Sharma ◽  
Bruce R. Stevens ◽  
Alexander G. Obukhov ◽  
Maria B. Grant ◽  
Gavin Y. Oudit ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Major Player

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B 0 AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.

scholarly journals Renin-Angiotensin System Blockade In The Coronavirus Disease 2019 Pandemic

2021 ◽  
Author(s):  
Jordana B Cohen ◽  
Andrew M South ◽  
Hossam A Shaltout ◽  
Matthew R Sinclair ◽  
Matthew A Sparks
Keyword(s):  
Viral Entry ◽  
Renin Angiotensin System ◽  
Adverse Outcomes ◽  
Host Cells ◽  
Protective Effects ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Epidemiologic Evidence

ABSTRACT In the early months of the coronavirus disease 2019 (COVID-19) pandemic, a hypothesis emerged suggesting that pharmacologic inhibitors of the renin-angiotensin system (RAS) may increase COVID-19 severity. This hypothesis was based on the role of angiotensin-converting enzyme 2 (ACE2), a counter-regulatory component of the RAS, as the binding site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), allowing viral entry into host cells. Extrapolations from prior evidence led to speculation that upregulation of ACE2 by RAS blockade may increase the risk of adverse outcomes from COVID-19. However, counterarguments pointed to evidence of potential protective effects of ACE2 and RAS blockade with regard to acute lung injury, as well as substantial risks from discontinuing these commonly used and important medications. Here we provide an overview of classic RAS physiology and the crucial role of ACE2 in systemic pathways affected by COVID-19. Additionally, we critically review the physiologic and epidemiologic evidence surrounding the interactions between RAS blockade and COVID-19. We review recently published trial evidence and propose important future directions to improve upon our understanding of these relationships.

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