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1.
Hypertension ; 76(5): 1350-1367, 2020 11.
Article in English | MEDLINE | ID: covidwho-2153223

ABSTRACT

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.


Subject(s)
Coronavirus Infections/epidemiology , Hypertension/epidemiology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Renin-Angiotensin System/physiology , Severe Acute Respiratory Syndrome/metabolism , Angiotensin-Converting Enzyme 2 , Blood Pressure Determination/methods , COVID-19 , China/epidemiology , Female , Humans , Hypertension/physiopathology , Incidence , Male , Pandemics/statistics & numerical data , Practice Guidelines as Topic , Prognosis , Research Design , Risk Assessment , Severe Acute Respiratory Syndrome/epidemiology
2.
Int J Mol Sci ; 23(22)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2143219

ABSTRACT

Coronavirus disease 2019 is caused by SARS-CoV-2 and is more severe in the elderly, racial minorities, and those with comorbidities such as hypertension and diabetes. These pathologies are often controlled with medications involving the renin-angiotensin-aldosterone system (RAAS). RAAS is an endocrine system involved in maintaining blood pressure and blood volume through components of the system. SARS-CoV-2 enters the cells through ACE2, a membrane-bound protein related to RAAS. Therefore, the use of RAAS inhibitors could worsen the severity of COVID-19's symptoms, especially amongst those with pre-existing comorbidities. Although a vaccine is currently available to prevent and reduce the symptom severity of COVID-19, other options, such as nitric oxide and hydrogen sulfide, may also have utility to prevent and treat this virus.


Subject(s)
COVID-19 , Hydrogen Sulfide , Hypertension , Humans , Aged , Renin-Angiotensin System/physiology , Hydrogen Sulfide/therapeutic use , Nitric Oxide , COVID-19/drug therapy , SARS-CoV-2 , Hypertension/drug therapy
3.
Toxicol Appl Pharmacol ; 456: 116267, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2117610

ABSTRACT

Organophosphates (OPs) are ubiquitous environmental contaminants, widely used as pesticides in agricultural fields. In addition, they serve as flame-retardants, plasticizers, antifoaming or antiwear agents in lacquers, hydraulic fluids, and floor polishing agents. Therefore, world-wide and massive application of these compounds have increased the risk of unintentional exposure to non-targets including the human beings. OPs are neurotoxic agents as they inhibit the activity of acetylcholinesterase at synaptic cleft. Moreover, they can fuel cardiovascular issues in the form of myocardities, cardiac oedema, arrhythmia, systolic malfunction, infarction, and altered electrophysiology. Such pathological outcomes might increase the severity of cardiovascular diseases which are the leading cause of mortality in the developing world. Coronavirus disease-19 (COVID-19) is the ongoing global health emergency caused by SARS-CoV-2 infection. Similar to OPs, SARS-CoV-2 disrupts cytokine homeostasis, redox-balance, and angiotensin-II/AT1R axis to promote cardiovascular injuries. Therefore, during the current pandemic milieu, unintentional exposure to OPs through several environmental sources could escalate cardiac maladies in patients with COVID-19.


Subject(s)
COVID-19 , Cardiovascular Diseases , Humans , Renin-Angiotensin System/physiology , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Organophosphates , Acetylcholinesterase , Peptidyl-Dipeptidase A/metabolism , Inflammation/chemically induced , Cardiovascular Diseases/chemically induced , Oxidative Stress
4.
Can Respir J ; 2022: 8698825, 2022.
Article in English | MEDLINE | ID: covidwho-2053441

ABSTRACT

Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the disease. The catalytic activity of cellular ACE2 (cACE2) and soluble ACE2 (sACE2) prevents angiotensin II and Des-Arg-bradykinin from accumulating in the body. On the other hand, SARS-CoV-2 mainly enters cells via cACE2. Thus, inhibition of ACE2 can prevent viral entry and reduce viral replication in host cells. The benefits of bradykinin inhibitors (BKs) have been reported in some COVID-19 clinical trials. Furthermore, the effects of cyclooxygenase (COX) inhibitors on ACE2 cleavage and prevention of viral entry into host cells have been reported in COVID-19 patients. However, the administration of COX inhibitors can reduce innate immune responses and have the opposite effect. A few studies suggest benefits of low-dose radiation therapy (LDR) in treating acute respiratory distress syndrome in COVID-19 patients. Nonetheless, radiation therapy can stimulate inflammatory pathways, resulting in adverse effects on lung injury in these patients. Overall, progress is being made in treating COVID-19 patients, but questions remain about which drugs will work and when. This review summarizes studies on the effects of a recombinant ACE2, BK and COX inhibitor, and LDR in patients with COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Angiotensin II/metabolism , Angiotensin II/pharmacology , Bradykinin/metabolism , Bradykinin/pharmacology , Bradykinin/therapeutic use , Humans , Peptidyl-Dipeptidase A/metabolism , Peptidyl-Dipeptidase A/therapeutic use , Prostaglandin-Endoperoxide Synthases/metabolism , Prostaglandin-Endoperoxide Synthases/pharmacology , Renin-Angiotensin System/physiology , SARS-CoV-2
5.
Int J Mol Sci ; 23(15)2022 Aug 04.
Article in English | MEDLINE | ID: covidwho-1969299

ABSTRACT

Dysregulation of renin-angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity and mortality. This study sought to investigate the effect of exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cells response in recovered COVID-19 patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang II and then stimulated with a SARS-CoV-2 peptide pool. T-cell responses were measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation was measured using a phosphokinase array. Our results showed that Ang II treatment significantly increased the magnitude of SARS-CoV-2-specific T-cell response in stimulated PBMCs with a SARS-CoV-2 peptide pool. Moreover, the phosphorylation levels of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increases in the presence of Ang II. The mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of T-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed increased productions of IL-1ß and IL-6 in Ang II-stimulated PBMCs without affecting the IL-10 level. To our knowledge, this study is the first to demonstrate that Ang II exaggerates SARS-CoV-2-specific T-cells response. Therefore, during COVID-19 infection, Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2 , Humans , Leukocytes, Mononuclear/metabolism , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , T-Lymphocytes
6.
J Cardiothorac Vasc Anesth ; 36(12): 4496-4500, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1956429

ABSTRACT

The renin-angiotensin-aldosterone system (RAAS), whose major vasopressor effector is angiotensin II (ATII), has multiple activities and regulates sodium-water homeostasis and fluid and blood pressure homeostasis. RAAS plays a crucial role in cardiocirculatory shock because it counteracts hypotension and hypovolemia by activating different physiologic responses. Based on the encouraging results of the ATHOS-3 trial, the US Food and Drug Administration and the European Medicines Agency approved the use of ATII for catecholamine-resistant vasodilatory shock. More recently, ATII was used for the compassionate treatment of critically ill patients with COVID-19. Beyond its vasopressor properties, ATII was hypothesized to have antiviral activity because it induces internalization and degradation of angiotensin-converting enzyme 2 receptors used by SARS-Cov-2 to infect cells. Overall, the use of ATII in patients with COVID-19 showed promising results because its administration was associated with the achievement and maintenance of target mean arterial pressure, increased PaO2/FIO2 ratio, and decreased FIO2. The aim of this narrative review is to summarize the available knowledge on the use of ATII in patients with COVID-19.


Subject(s)
COVID-19 , Sepsis , Humans , SARS-CoV-2 , Angiotensin II/therapeutic use , Renin-Angiotensin System/physiology , Vasoconstrictor Agents/therapeutic use , Vasoconstrictor Agents/pharmacology , Sepsis/drug therapy
7.
Cells ; 11(13)2022 07 02.
Article in English | MEDLINE | ID: covidwho-1933987

ABSTRACT

SARS-CoV-2 infection leads to severe lung damage due to pneumonia and, in more severe cases, leads to acute respiratory distress syndrome, or ARDS. This affects the viability of bronchoalveolar cells. An important role in the pathogenesis of these complications is the hyperactivation of the renin-angiotensin-aldosterone (RAA) pathway and induction of cytokine storm that occurs in an Nlrp3 inflammasome-dependent manner. To shed more light on the susceptibility of lung tissue to SARS-CoV-2 infection, we evaluated murine bronchioalveolar stem cells (BASC), alveolar type II cells (AT2), and 3D-derived organoids expression of mRNA encoding genes involved in virus entry into cells, components of RAA, and genes that comprise elements of the Nlrp3 inflammasome pathway. We noticed that all these genes are expressed by lung alveolar stem cells and organoids-derived from these cells. Interestingly, all these cells express a high level of ACE2 that, on the one hand, serves as an entry receptor for SARS-CoV-2 and, on the other, converts angiotensin II into its physiological antagonist, angiotensin 1-7 (Ang 1-7), which has been reported to have a protective role in lung damage. To shed more light on the role of Ang 1-7 on lung tissue, we exposed lung-derived BASC and AT2 cells to this mediator of RAA and noticed that it increases the proliferation of these cells. Based on this, Ang 1-7 could be employed to alleviate the damage to lung alveolar stem/progenitor cells during SARS-CoV-2 infection.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Angiotensin I , Angiotensin-Converting Enzyme 2 , Animals , Cell Proliferation , Inflammasomes/metabolism , Lung/metabolism , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Peptide Fragments , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
8.
Neurotox Res ; 40(5): 1586-1596, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1930582

ABSTRACT

The outbreak of SARs-CoV-2 with emerging new variants is leading to global health crisis and has brought a major concern for patients with comorbidities. Parkinson's disease (PD) is a motor neurodegenerative disease involving various metabolic and psychological ailments along with the common occurrence of hyposmia as observed in COVID-19 patients. In addition, the observed surplus inflammatory responses in both diseases are also alarming. Alongside, angiotensin-converting enzyme 2 (ACE2) receptor, essentially required by SARS-CoV-2 to enter the cell and dopamine decarboxylase (DDC), required for dopamine synthesis is known to co-regulate in the non-neuronal cells. Taken together, these conditions suggested the probable reciprocal pathological relation between COVID-19 and PD and also suggested that during comorbidities, the disease diagnosis and therapeutics are critical and may engender severe health complications. In this review, we discuss various events and mechanisms which may have implications for the exacerbation of PD conditions and must be taken into account during the treatment of patients.


Subject(s)
COVID-19 , Carboxy-Lyases , Neurodegenerative Diseases , Parkinson Disease , Angiotensin-Converting Enzyme 2 , COVID-19/complications , Carboxy-Lyases/metabolism , Dopamine , Humans , Parkinson Disease/complications , Parkinson Disease/epidemiology , Parkinson Disease/therapy , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
9.
Mol Biol Rep ; 49(8): 8131-8137, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1926051

ABSTRACT

Increasing evidence strongly support that the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the development of COVID-19-associated central nervous system (CNS) manifestations. The presence of SARS-CoV-2 viral protein in the brainstem, which includes cardiovascular control centers, has been documented previously. Given the changes in autonomic nervous system function evaluated by heart rate variability (HRV) metrics, which are observed even prior to clinical signs, the potential effect of SARS-CoV-2 on the autonomic nervous system (ANS) center is likely. The integral parts of the brain renin-angiotensin system, as ACE2 enzyme, are highly expressed in the brainstem, which may also be involved in baroreflex sensitivity, playing an important role in HRV. SARS-CoV-2 may bind to ACE2 in order to enter the host brainstem cell and change baroreflex sensitivity due to the altered ratio of the concentration of angiotensin II (Ag II) to angiotensin (1-7). In this article, we discussed the information on the possibility that the SARS-CoV-2 viral particle by disrupting the homeostasis of the brain renin-angiotensin system even without brainstem neuropathological changes, may affect the function of the ANS center in the brainstem. SARS-CoV-2 could influence ANS function before affecting the immune system. It is possible that the altered HRV parameters imply the potential neurotropic characteristics of SARS-CoV-2. Therefore, this potential feature should be taken into account in diagnostic and therapeutic approaches for COVID-19 patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Autonomic Nervous System/metabolism , Heart Rate , Humans , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology
10.
Front Cell Infect Microbiol ; 12: 896972, 2022.
Article in English | MEDLINE | ID: covidwho-1902936

ABSTRACT

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.


Subject(s)
COVID-19 , Hemostasis , Humans , Pandemics , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
11.
Curr Hypertens Rep ; 24(10): 425-433, 2022 10.
Article in English | MEDLINE | ID: covidwho-1899316

ABSTRACT

PURPOSE OF REVIEW: This review summarises the literature data and provides an overview of the role and impact of the use of renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with coronavirus disease 2019 (COVID-19) infection. RECENT FINDINGS: The angiotensin-converting enzyme 2 (ACE2) has a key role in the regulation of the RAAS pathway, downregulating angiotensin II and attenuating inflammation, vasoconstriction and oxidative stress. Additionally, it plays an instrumental part in COVID-19 infection as it facilitates the cell entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enables its replication. The use and role of RAAS inhibitors therefore during the COVID-19 pandemic have been intensively investigated. Although it was initially assumed that RAAS inhibitors may relate to worse clinical outcomes and severe disease, data from large studies and meta-analyses demonstrated that they do not have an adverse impact on clinical outcomes or prognosis. On the contrary, some experimental and retrospective observational cohort studies showed a potential protective mechanism, although this effect remains to be seen in large clinical trials.


Subject(s)
COVID-19 , Hypertension , Aldosterone/metabolism , Angiotensin II/metabolism , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , Humans , Hypertension/drug therapy , Mineralocorticoid Receptor Antagonists/therapeutic use , Pandemics , Peptidyl-Dipeptidase A/metabolism , Renin/metabolism , Renin-Angiotensin System/physiology , Retrospective Studies , SARS-CoV-2
12.
Environ Sci Pollut Res Int ; 29(38): 57040-57053, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1899268

ABSTRACT

Obesity is a term that has recently been referred to describe a condition in which a person has become a diseased vessel. Obesity's internal pathology is too mysterious as it has a close resemblance with fatal diseases pathology. Obesity and coronavirus disease 2019 (COVID-19) are simultaneous epidemics declared by many organizations after observing their rampage in the recent world. Oxidative stress, cytokine storm, interleukin, and their contribution to the internal adipocyte environment implicated in the cascades of inflammatory pathology are portrayed here. Major determinants like angiotensin-converting enzyme 2 (ACE2) and renin-angiotensin-aldosterone system (RAAS) axis are highly sensitive molecular factors. Data from various countries suggested a clinical overview of how greater body mass index (BMI) is related to greater COVID-19 risk. It also gives insight into how obese individuals are obligately getting admitted and combating COVID-19 in intensive care unit including children less than 13 years of age under ultimate therapeutic options. There are numerous studies currently taking place for finding a cure for obesity which are mainly focused on natural resources and novel therapies like photobiomodulation (PBM) consisting of laser treatment, infrared treatment, etc. as current pharmacological treatments are reported to have fatal adverse effects. Finally, it is discussed how attenuating obesity will be a solution for future combat strategy. This review gives light on the areas of coagulation, inflammatory parameters, cardiometabolic complications, endothelial dysfunctions, immunological infirmity due to COVID-19 in obese individuals. A conceptual outline about correlation between the inflammatory pathophysiological steps triggering the aggravation of fatal consequences has been drawn in this review.


Subject(s)
COVID-19 , Child , Humans , Obesity , Peptidyl-Dipeptidase A/metabolism , Peptidyl-Dipeptidase A/pharmacology , Renin-Angiotensin System/physiology , SARS-CoV-2
13.
Acta Histochem ; 124(5): 151908, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1866763

ABSTRACT

Cytokine storms and extra-activated cytokine signaling pathways can lead to severe tissue damage and patient death. Activation of inflammatory signaling pathways during Cytokine storms are an important factor in the development of acute respiratory syndrome (SARS-CoV-2), which is the major health problem today, causing systemic and local inflammation. Cytokine storms attract many inflammatory cells that attack the lungs and other organs and cause tissue damage. Angiotensin-converting enzyme 2 (ACE2) are expressed in a different type of tissues. inhibition of ACE2 activity impairs renin-angiotensin (RAS) function, which is related to the severity of symptoms and mortality rate in COVID-19 patients. Different signaling cascades are activated, affecting various organs during SARS-CoV-2 infection. Nowadays, there is no specific treatment for COVID-19, but scientists have recognized and proposed several treatment alternatives, including applying cytokine inhibitors, immunomodulators, and plasma therapy. Herein, we have provided the detailed mechanism of SARS-CoV-2 induced cytokine signaling and its connection with pathophysiological features in different organs. Possible treatment options to cope with the severe clinical manifestations of COVID-19 are also discussed.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokines/metabolism , Humans , Renin-Angiotensin System/physiology , SARS-CoV-2 , Signal Transduction
14.
Crit Care Med ; 50(9): 1306-1317, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-1860941

ABSTRACT

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup ( n = 46), recorded d -dimer ( n = 967), comparing males with females. SETTING: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces. PATIENTS: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation ( p = 0.006) and vasopressors ( p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females. CONCLUSIONS: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.


Subject(s)
COVID-19 , Hypertension , Angiotensin II/pharmacology , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , Canada , Female , Humans , Male , Prospective Studies , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Sex Characteristics
15.
Circ Res ; 130(10): 1618-1641, 2022 05 13.
Article in English | MEDLINE | ID: covidwho-1846593

ABSTRACT

Viruses are ubiquitous in the environment and continue to have a profound impact on human health and disease. The COVID-19 pandemic has highlighted this with impressive morbidity and mortality affecting the world's population. Importantly, the link between viruses and hypertension, cardiovascular disease, and kidney disease has resulted in a renewed focus and attention on this potential relationship. The virus responsible for COVID-19, SARS-CoV-2, has a direct link to one of the major enzymatic regulatory systems connected to blood pressure control and hypertension pathogenesis, the renin-angiotensin system. This is because the entry point for SARS-CoV-2 is the ACE2 (angiotensin-converting enzyme 2) protein. ACE2 is one of the main enzymes responsible for dampening the primary effector peptide Ang II (angiotensin II), metabolizing it to Ang-(1-7). A myriad of clinical questions has since emerged and are covered in this review. Several other viruses have been linked to hypertension, cardiovascular disease, and kidney health. Importantly, patients with high-risk apolipoprotein L1 (APOL1) alleles are at risk for developing the kidney lesion of collapsing glomerulopathy after viral infection. This review will highlight several emerging viruses and their potential unique tropisms for the kidney and cardiovascular system. We focus on SARS-CoV-2 as this body of literature in regards to cardiovascular disease has advanced significantly since the COVID-19 pandemic.


Subject(s)
COVID-19 , Cardiovascular Diseases , Hypertension , Kidney Diseases , Angiotensin-Converting Enzyme 2 , Apolipoprotein L1/metabolism , Cardiovascular Diseases/epidemiology , Female , Humans , Hypertension/epidemiology , Kidney Diseases/epidemiology , Male , Pandemics , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
16.
Molecules ; 27(9)2022 May 02.
Article in English | MEDLINE | ID: covidwho-1820343

ABSTRACT

COVID-19 has expanded across the world since its discovery in Wuhan (China) and has had a significant impact on people's lives and health. Long COVID is a term coined by the World Health Organization (WHO) to describe a variety of persistent symptoms after acute SARS-CoV-2 infection. Long COVID has been demonstrated to affect various SARS-CoV-2-infected persons, independently of the acute disease severity. The symptoms of long COVID, like acute COVID-19, consist in the set of damage to various organs and systems such as the respiratory, cardiovascular, neurological, endocrine, urinary, and immune systems. Fatigue, dyspnea, cardiac abnormalities, cognitive and attention impairments, sleep disturbances, post-traumatic stress disorder, muscle pain, concentration problems, and headache were all reported as symptoms of long COVID. At the molecular level, the renin-angiotensin system (RAS) is heavily involved in the pathogenesis of this illness, much as it is in the acute phase of the viral infection. In this review, we summarize the impact of long COVID on several organs and tissues, with a special focus on the significance of the RAS in the disease pathogenesis. Long COVID risk factors and potential therapy approaches are also explored.


Subject(s)
COVID-19 , Angiotensin-Converting Enzyme 2 , COVID-19/complications , Humans , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
17.
Molecules ; 27(8)2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1810037

ABSTRACT

(1) Background: ACE and CPN serum activity correlated with disease severity in an earlier study of 45 hospitalized COVID-19 patients. The serum protein profile was investigated in the same cohort here to shed more light on the involvement of the renin-angiotensin system (RAS). (2) Methods: High-definition mass spectrometry-based protein expression analysis was performed, followed by multivariate statistical and network analyses. (3) Results: The protein profiles of hospitalized patients (HoP) differed significantly from those of convalescent and healthy probands. Surprisingly, HoP samples separated into six groups according to their protein profiles: group (G) 1 represented the youngest and the least afflicted patients, and G6 the oldest and critically ill patients. At least two major pathophysiological schemes were indicated based on differing involvement of the kallikrein-kinin system (KKS), the RAS and complement activation. The serum angiotensinogen concentration increased with disease severity. (4) Conclusions: The important role of the RAS in the response to COVID-19 infection was substantiated, but other pathways such as the KKS, plasminogen activation and complement activation influence the systemic response to the infection.


Subject(s)
COVID-19 , Renin-Angiotensin System , Angiotensinogen/metabolism , COVID-19/complications , Humans , Peptidyl-Dipeptidase A/metabolism , Proteomics , Renin-Angiotensin System/physiology , Severity of Illness Index
18.
Int J Mol Sci ; 23(7)2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1785737

ABSTRACT

Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The renin-angiotensin system is involved in the physiopathology of stroke and has an essential impact on hypertension as a risk factor. This article targeted the role of the renin-angiotensin system in stroke neuroprotection by reviewing the current literature available. The mechanism of action of the renin-angiotensin system was observed through the effects on AT1, AT2, and Mas receptors. The neuroprotective properties ascertained by angiotensin in stroke seem to be independent of the blood pressure reduction mechanism, and include neuroregeneration, angiogenesis, and increased neuronal resistance to hypoxia. The future relationship of stroke and the renin-angiotensin system is full of possibilities, as new agonist molecules emerge as potential candidates to restrict the impairment caused by stroke.


Subject(s)
Hypertension , Stroke , Humans , Hypertension/drug therapy , Neuroprotection , Renin-Angiotensin System/physiology , Stroke/drug therapy , Stroke/prevention & control
19.
Eur Rev Med Pharmacol Sci ; 26(6): 2171-2178, 2022 03.
Article in English | MEDLINE | ID: covidwho-1776796

ABSTRACT

Several receptors for the angiotensin-converting enzyme 2 (ACE2), essential for the penetration of SARS-CoV-2 into cells, are located in the tissues of the endocrine glands. Therefore, it has been suggested that SARS-CoV-2 infection results in the development of hormonal disturbances. To date, several cases of endocrine disturbances related to the dysfunction of all endocrine glands during and after SARS-CoV-2 infection have been described. In this review, we discuss the endocrine system disturbances in patients with COVID-19 and post-COVID-19 syndrome. Based on the case reports described in the literature, patients with COVID-19 may develop endocrine disturbances that are immediately life-threatening. In addition, patients with post-COVID-19 syndrome may develop chronic endocrine disturbances. In summary, the diagnostics of endocrine system disturbances based on clinical symptoms should be taken into account in both patients with COVID-19 and post-COVID-19 syndrome.


Subject(s)
COVID-19 , COVID-19/complications , Endocrine System/metabolism , Humans , Peptidyl-Dipeptidase A/metabolism , Renin-Angiotensin System/physiology , SARS-CoV-2
20.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(1): 52-62, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1719686

ABSTRACT

The renin-angiotensin system (RAS) is one of the most complex hormonal regulatory systems, involving several organs that interact to regulate multiple body functions. The study of this system initially focused on investigating its role in the regulation of both cardiovascular function and related pathologies. From this approach, pharmacological strategies were developed for the treatment of cardiovascular diseases. However, new findings in recent decades have suggested that the RAS is much more complex and comprises two subsystems, the classic RAS and an alternative RAS, with antagonistic effects that are usually in equilibrium. The classic system is involved in pathologies where inflammatory, hypertrophic and fibrotic phenomena are common and is related to the development of chronic diseases that affect various body systems. This understanding has been reinforced by the evidence that local renin-angiotensin systems exist in many tissue types and by the role of the RAS in the spread and severity of COVID-19 infection, where it was discovered that viral entry into cells of the respiratory system is accomplished through binding to angiotensin-converting enzyme 2, which is present in the alveolar epithelium and is overexpressed in patients with chronic cardiometabolic diseases. In this narrative review, preclinical and clinical aspects of the RAS are presented and topics for future research are discussed some aspects are raised that should be clarified in the future and that call for further investigation of this system.


Subject(s)
COVID-19 , Cardiovascular Diseases , Humans , Renin-Angiotensin System/physiology , SARS-CoV-2
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