Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.111
Filtrar
1.
Int J Mol Sci ; 21(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33138181

RESUMO

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.


Assuntos
Lesão Pulmonar Aguda/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/patologia , Síndrome Respiratória Aguda Grave/patologia , Vasoconstrição/fisiologia , Betacoronavirus , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Sistema Calicreína-Cinina/fisiologia , Pandemias , Sistema Renina-Angiotensina/fisiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Vasoconstrição/efeitos dos fármacos
3.
J Renin Angiotensin Aldosterone Syst ; 21(4): 1470320320972018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33169644

RESUMO

In the wake of the COVID-19 pandemic it has become clear that there is a need for therapies that are capable of reducing damage caused to patients from infections. Infections that induce Acute Respiratory Distress Syndrome (ARDS) are especially devastating because lung damage is so critical and difficult to manage. Angiotensin (1-7) [A(1-7)] has already been shown to protect pulmonary health and architecture in various models of disease. There is also evidence that A(1-7) can modulate immune function and protect various organs (lung, kidney, and heart) from oxidative damage and inflammation. Here we focus on making a case for the development of novel therapies that target the protective arm of the Renin Angiotensin System (RAS).


Assuntos
Angiotensina I/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/virologia , Angiotensina I/fisiologia , Animais , Infecções por Coronavirus/mortalidade , Humanos , Pandemias , Fragmentos de Peptídeos/fisiologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
5.
Rev. clín. esp. (Ed. impr.) ; 220(8): 507-510, nov. 2020.
Artigo em Espanhol | IBECS | ID: ibc-192189

RESUMO

La eclosión de la pandemia por COVID-19 supone un reto de enormes dimensiones y, dada la gran presencia de diabetes mellitus tipo2 en la población actual, hace que sea un problema de salud en el que centrar nuestros esfuerzos para dar la mejor respuesta a nuestros pacientes, que son más vulnerables al desarrollo de la infección y candidatos a presentar cuadros clínicos más graves. Este documento pretende abordar la relación entre la infección por COVID-19 y la DM2. Para ello analizaremos brevemente qué datos epidemiológicos sustentan esta asociación y, posteriormente, se profundizará en los mecanismos fisiopatológicos que podrían conectar ambas enfermedades


The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the two diseases


Assuntos
Humanos , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/complicações , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Peptidil Dipeptidase A/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Peptídeos Semelhantes ao Glucagon/agonistas , Insulina/metabolismo , Indicadores de Morbimortalidade , Sistema Renina-Angiotensina/fisiologia
6.
J Diabetes Res ; 2020: 8205261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134395

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.


Assuntos
Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Doenças Endêmicas , Malária/epidemiologia , Pneumonia Viral/epidemiologia , África/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Humanos , Resistência à Insulina/fisiologia , Malária/complicações , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/patologia , Estado Pré-Diabético/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
7.
Int J Mol Sci ; 21(21)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126657

RESUMO

Acute respiratory distress syndrome (ARDS) is characterized by massive inflammation, increased vascular permeability and pulmonary edema. Mortality due to ARDS remains very high and even in the case of survival, acute lung injury can lead to pulmonary fibrosis. The renin-angiotensin system (RAS) plays a significant role in these processes. The activities of RAS molecules are subject to dynamic changes in response to an injury. Initially, increased levels of angiotensin (Ang) II and des-Arg9-bradykinin (DABK), are necessary for an effective defense. Later, augmented angiotensin converting enzyme (ACE) 2 activity supposedly helps to attenuate inflammation. Appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair. ACE2 has been identified as a common target for different pathogens. Some Coronaviruses, including SARS-CoV-2, also use ACE2 to infiltrate the cells. A number of questions remain unresolved. The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-α (TNF-α)-signaling is unclear. The roles of other non-classical RAS-associated molecules, e.g., alamandine, Ang A or Ang 1-9, also deserve attention. In addition, the impact of established RAS-inhibiting drugs on the pulmonary RAS is to be elucidated. The unfavorable prognosis of ARDS and the lack of effective treatment urge the search for novel therapeutic strategies. In the context of the ongoing SARS-CoV-2 pandemic and considering the involvement of humoral disbalance in the pathogenesis of ARDS, targeting the renin-angiotensin system and reducing the pathogen's cell entry could be a promising therapeutic strategy in the struggle against COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/patologia , Sistema Renina-Angiotensina/fisiologia , Síndrome Respiratória Aguda Grave/patologia , Proteína ADAM17/metabolismo , Animais , Betacoronavirus , Permeabilidade Capilar/fisiologia , Humanos , Inflamação/patologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Pandemias , Edema Pulmonar/patologia , Ratos , Fator de Necrose Tumoral alfa/metabolismo
9.
PLoS One ; 15(10): e0240647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112891

RESUMO

The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.


Assuntos
Betacoronavirus/fisiologia , Biologia Computacional , Infecções por Coronavirus/virologia , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Envelhecimento/metabolismo , Sítios de Ligação , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Ontologia Genética , Humanos , Interferons/fisiologia , Pulmão/metabolismo , Masculino , Metaloproteases/biossíntese , Metaloproteases/genética , Neovascularização Fisiológica/fisiologia , Especificidade de Órgãos , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/genética , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , Receptores Virais/biossíntese , Receptores Virais/genética , Sistema Renina-Angiotensina/fisiologia , Caracteres Sexuais , Análise de Célula Única , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Ligação Viral
11.
Heart Lung Circ ; 29(11): 1596-1602, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32972810

RESUMO

The recently described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people, with thousands of fatalities. It has prompted global efforts in research, with focus on the pathophysiology of coronavirus disease-19 (COVID-19), and a rapid surge of publications. COVID-19 has been associated with a myriad of clinical manifestations, including the lungs, heart, kidneys, central nervous system, gastrointestinal system, skin, and blood coagulation abnormalities. The endothelium plays a key role in organ dysfunction associated with severe infection, and current data suggest that it is also involved in SARS-CoV-2-induced sepsis. This critical review aimed to address a possible unifying mechanism underlying the diverse complications of COVID-19: microvascular dysfunction, with emphasis on the renin-angiotensin system. In addition, research perspectives are suggested in order to expand understanding of the pathophysiology of the infection.


Assuntos
Infecções por Coronavirus , Microvasos , Pandemias , Pneumonia Viral , Sistema Renina-Angiotensina/fisiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Humanos , Microvasos/metabolismo , Microvasos/fisiopatologia , Microvasos/virologia , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia
12.
Hypertension ; 76(5): 1350-1367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32981369

RESUMO

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.


Assuntos
Infecções por Coronavirus/epidemiologia , Hipertensão/epidemiologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Sistema Renina-Angiotensina/fisiologia , Síndrome Respiratória Aguda Grave/metabolismo , Determinação da Pressão Arterial/métodos , China/epidemiologia , Feminino , Humanos , Hipertensão/fisiopatologia , Incidência , Masculino , Pandemias/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Prognóstico , Projetos de Pesquisa , Medição de Risco , Síndrome Respiratória Aguda Grave/epidemiologia
13.
Intern Med ; 59(18): 2237-2244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32938851

RESUMO

Objective The intrarenal renin-angiotensin system (RAS) is activated in chronic kidney disease (CKD) patients and is not suppressed at night in CKD patients showing nocturnal hypertension, contributing to renal damage. Furthermore, changes in RAS inhibitor administration from morning to evening, namely chronotherapy, ameliorates renal damage at night. We attempted to clarify whether or not chronotherapy ameliorates renal damage by suppressing the intrarenal RAS activity. Methods We recruited 34 CKD patients with RAS inhibitors in the morning. We conducted ambulatory blood pressure (BP) monitoring and urine collection and evaluated urinary albumin (Alb) and angiotensinogen (AGT), which are surrogate markers for intrarenal RAS activity during the day and at night, respectively. The same experiments were conducted after changing the administration time. The ratio of values associated with morning versus evening dosing was defined as the morning to evening (M/E) ratio. Results The M/E ratio of urinary Alb had a significant and positive relationship with that of urinary AGT during the day and at night in all CKD patients. However, no significant relationships were found between the M/E ratios of urinary Alb and AGT using multiple linear regression analyses. Conversely, there was a significant and positive relationship between the M/E ratios of urinary Alb and AGT at night but not during the day in CKD patients whose estimated glomerular filtration rate was <45 mL/min/1.73 m2 and whose night-to-day ratio of systolic BP was >0.90, even after adjustment. Conclusion This study indicated that chronotherapy with RAS inhibitors improved the renal damage via intrarenal RAS suppression, especially in CKD patients with an impaired renal function and nocturnal hypertension.


Assuntos
Cronoterapia Farmacológica , Rim/fisiopatologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Albuminúria , Angiotensinogênio/urina , Biomarcadores/sangue , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal/complicações , Sistema Renina-Angiotensina/fisiologia
14.
Medwave ; 20(7): e8008, 2020 Aug 28.
Artigo em Espanhol | MEDLINE | ID: mdl-32877391

RESUMO

In December 2019, a new strain of the SARS-CoV-2 coronavirus was reported in Wuhan, China, which produced severe lung involvement and progressed to respiratory distress. To date, more than seventeen million confirmed cases and more than half a million died worldwide from COVID-19. Patients with cardiovascular disease are more susceptible to contracting this disease and presenting more complications. We did a literature search on the association of cardiovascular disease and COVID-19 in databases such as Scopus, PubMed/MEDLINE, and the Cochrane Library. The purpose of this review is to provide updated information for health professionals who care for patients with COVID-19 and cardiovascular disease, given that they have a high risk of complications and mortality. Treatment with angiotensin-converting enzyme inhibitors and receptor blockers is controversial, and there is no evidence not to use these medications in patients with COVID-19. Regarding treatment with hydroxychloroquine associated or not with azithromycin, there is evidence of a higher risk with its use than clinical benefit and decreased mortality. Likewise, patients with heart failure are an important risk group due to their condition per se. Patients with heart failure and COVID-19 are a diagnostic dilemma because the signs of acute heart failure could be masked. On the other hand, in patients with acute coronary syndrome, the initial therapeutic approach could change in the context of the pandemic, although only based on expert opinions. Nonetheless, many controversial issues will be the subject of future research.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/terapia , Algoritmos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Quimioterapia Combinada , Eletrocardiografia/efeitos dos fármacos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Hidroxicloroquina/efeitos adversos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Prognóstico , Sistema Renina-Angiotensina/fisiologia
15.
J Chin Med Assoc ; 83(9): 812-816, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902940

RESUMO

The 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) is a pandemic disease worldwide. The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is continuing at a rapid speed. Till May 4, 2020, there have been 3,407,747 confirmed cases and 238,198 deaths globally. The common symptoms in pregnant women are fever, cough, and dyspnea. Angiotensin-converting enzyme 2 (ACE2) has transient overexpression and increased activity during pregnancy, which is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. There is no evidence that pregnant women are more susceptible to SARS-CoV-2. To date, there is no valid medication or vaccination. The immune suppression or modulation during pregnancy increases the risk of severe pneumonia. Remdesivir is an antiviral medication targeting ribonucleic acid (RNA) synthesis that has clinical improvement in the treatment of SARS-CoV-2. Chloroquine is controversial in its effectiveness and safety to treat SARS-CoV-2. Remdesivir is safe in pregnancy. Chloroquine has not been formally assigned to a pregnancy category by the Food and Drug Administration (FDA). The management strategy includes monitoring fetal heart rate and uterine contractions; early oxygenation if O2 saturation is less than 95%; empiric antibiotics for prevention of secondary infection; corticosteroid to treat maternal SARS-CoV-2 disease routinely is not suggested, only for fetal lung maturation in selected cases; and consideration of delivery is according to the obstetric indication, gestational age, and severity of the disease. During epidemics, delivery at 32-34 weeks is considered. The indication for the Cesarean section should be flexible to minimize the risk of infection during the delivery. The newborn should be in isolation ward immediately after birth; breastfeeding is not contraindicated but should avoid direct transmission infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Recém-Nascido , Pandemias , Pneumonia Viral/epidemiologia , Gravidez , Sistema Renina-Angiotensina/fisiologia
17.
Clin Sci (Lond) ; 134(18): 2489-2501, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32990314

RESUMO

Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin-angiotensin system (RAS) and providing a cardioprotective role. Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. However, it does convert a number of other regulatory peptides in vitro and in vivo. Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Angiotensina II/efeitos dos fármacos , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Infecções por Coronavirus/metabolismo , Humanos , Pandemias , Pneumonia Viral/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Vasoconstritores/farmacologia
18.
Mol Neurobiol ; 57(12): 4921-4928, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32813238

RESUMO

The global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore and examine the possible links between COVID-19 and ischemic stroke (IS). Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. The swift increase in the knowledge of SARS-CoV-2 has given creditable evidence that SARS-CoV-2 infected patients also encounter neurological deficits. As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra. The COVID-19 pandemic has affected people with various pre-existing diseases, including IS, in such a way that these patients need special care and attention for their survival. Several clinical trials are currently ongoing worldwide as well as many other projects are in different stages of conceptualization and planning to facilitate the effective management of stroke patients with COVID-19 infection.


Assuntos
Betacoronavirus , Isquemia Encefálica/etiologia , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Acidente Vascular Cerebral/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Barreira Hematoencefálica , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Quimiotaxia de Leucócito , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Encefalite Viral/complicações , Encefalite Viral/fisiopatologia , Hemodinâmica , Humanos , Inflamação , Modelos Imunológicos , Modelos Neurológicos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Receptores Virais/fisiologia , Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia
19.
Int J Cardiol ; 321: 150-154, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32738257

RESUMO

A role for the renin-angiotensin-aldosterone-system in Severe Acute Respiratory Syndrome-Coronavirus-2 infection and in the development of COronaVIrus Disease-19 disease has generated remarkable concerns among physicians and patients. Even though a suggestive pathophysiological link between renin-angiotensin-aldosterone-system and the virus has been proposed, its pathogenic role remains very difficult to be defined. Although COronaVIrus Disease-19 targets preferentially older people with high prevalence of hypertension and extensive use of renin-angiotensin-aldosterone-system inhibitors, an independent role for hypertension and its therapies is not defined. In this article, we scrutinize evidence from the most representative available studies in which the potential role of renin-angiotensin system inhibitors, specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, was evaluated in the COronaVIrus Disease-19 disease course, with regard to severity of the disease and mortality. We conclude that at this time, the overall available evidence fails to support a pathogenetic speaks against any harmful role for of renin-angiotensin-aldosterone-system inhibitors in COronaVIrus Disease-19. Consequently, we conclude that treatment with renin-angiotensin-aldosterone-system inhibitors should not be discontinued and, therefore, these therapies should not be interrupted.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Betacoronavirus/fisiologia , Infecções por Coronavirus , Hipertensão/tratamento farmacológico , Pandemias , Pneumonia Viral , Sistema Renina-Angiotensina , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
20.
J Cardiovasc Pharmacol Ther ; 25(6): 503-507, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32748634

RESUMO

To determine the effect renin-angiotensin system blockers on the outcome in patients with hypertension and concurrent COVID-19 infection, we searched PubMed, the Cochrane Library, and Google Scholar for relevant articles. Twelve studies with a total of 16,101 patients met the inclusion criteria. The mortality rate among the users of angiotensin converting enzyme inhibitors or angiotensin receptor blockers was 12.15% and in non-users it was 14.56% (risk ratio 0.70, 95% CI [0.53-0.91], P < 0.007). There was no difference in the risk of death between the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (risk ratio 1.09, 95% CI [0.90 -1.32]). We conclude that the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers improves mortality in patients with hypertension and concurrent COVID-19 infection, without a significant difference between ACEIs and ARBs in this population.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pneumonia Viral/epidemiologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II , Betacoronavirus , Infecções por Coronavirus/mortalidade , Humanos , Pandemias , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA