Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.215
Filtrar
1.
JAAPA ; 34(12): 15-20, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34772853

RESUMO

ABSTRACT: Resistant hypertension affects about 17% of the US population. However, it is difficult to diagnose because of multiple factors that influence adequate treatment of BP, including patient lifestyle and comorbidities, improper therapeutic regimens, and secondary mechanisms. Possible causes of resistant hypertension include nonmodulator hypertension, which affects patients who have an inappropriate response to elevated sodium through the renin-angiotensin-aldosterone system. Early identification and frequent follow-up can help patients achieve BP goals more rapidly and may reduce morbidity and mortality associated with complications of hypertension, including cerebrovascular accident, cardiovascular disease, and kidney disease.


Assuntos
Doenças Cardiovasculares , Hipertensão , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Sistema Renina-Angiotensina
2.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769350

RESUMO

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin-angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.


Assuntos
COVID-19/patologia , Células Endoteliais/metabolismo , COVID-19/complicações , COVID-19/virologia , Síndrome da Liberação de Citocina/etiologia , Células Endoteliais/citologia , Células Endoteliais/virologia , Insuficiência Cardíaca/etiologia , Humanos , Insuficiência Renal/etiologia , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2/isolamento & purificação , Trombose/etiologia
3.
Front Endocrinol (Lausanne) ; 12: 725967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745001

RESUMO

The renin-angiotensin system (RAS) is crucially involved in the physiology and pathology of all organs in mammals. Angiotensin-converting enzyme 2 (ACE2), which is a homolog of ACE, acts as a negative regulator in the homeostasis of RAS. ACE2 has been proven to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic. As SARS-CoV-2 enters the host cells through binding of viral spike protein with ACE2 in humans, the distribution and expression level of ACE2 may be critical for SARS-CoV-2 infection. Growing evidence shows the implication of ACE2 in pathological progression in tissue injury and several chronic conditions such as hypertension, diabetes, and cardiovascular disease; this suggests that ACE2 is essential in the progression and clinical prognosis of COVID-19 as well. Therefore, we summarized the expression and activity of ACE2 under various conditions and regulators. We further discussed its potential implication in susceptibility to COVID-19 and its potential for being a therapeutic target in COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/prevenção & controle , Peptidil Dipeptidase A/fisiologia , Sistema Renina-Angiotensina/fisiologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Humanos , Terapia de Alvo Molecular , Pandemias , SARS-CoV-2
4.
Int J Mol Sci ; 22(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34769093

RESUMO

The renin-angiotensin system (RAS) is a key regulator of blood pressure and hypertension. Angiotensin-converting enzyme 2 (ACE2) and angiotensin-converting enzyme I (ACE) are two main components of the RAS that play a major role in blood pressure homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 as a receptor to enter cells. Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19. In our previous studies, we produced and identified peptide sequences present in whey hydrolysates exhibiting high ACE inhibitory activity. Therefore, the aim of this work is to obtain an improved understanding of the function of these natural peptides as RAS inhibitors and investigate their potential therapeutic role in the COVID-19 pandemic. The molecular interactions between peptides IPP, LIVTQ, IIAE, LVYPFP, and human ACE2 were assessed by employing a molecular docking approach. The results show that natural whey-derived peptides have a dual inhibitory action against both ACE and ACE2. This dual activity distinguishes these ACE inhibitory peptides from synthetic drugs, such as Captopril and Lisinopril which were not shown to inhibit ACE2 activity, and may represent a potential strategy in the treatment of COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19 , Peptídeos/química , Peptídeos/farmacologia , Enzima de Conversão de Angiotensina 2/química , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais/química , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptidil Dipeptidase A/química , Sistema Renina-Angiotensina/efeitos dos fármacos , Proteínas do Soro do Leite/química
5.
ASN Neuro ; 13: 17590914211057635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755562

RESUMO

Among the plethora of debilitating neurological disorders of COVID-19 syndrome in survivors, the scope of SARS-CoV-2-induced dysautonomia (DNS) is yet to be understood, though the implications are enormous. Herein, we present an inclusive mini-review of SARS-CoV-2-induced DNS and its associated complications. Although, the direct link between Covid-19 and DSN is still speculative, the hypothetical links are thought to be either a direct neuronal injury of the autonomic pathway or a para/post-infectious immune-induced mechanism. SARS-CoV-2 infection-induced stress may activate the sympathetic nervous system (SNS) leading to neuro-hormonal stimulation and activation of pro-inflammatory cytokines with further development of sympathetic storm. Sympathetic over-activation in Covid-19 is correlated with increase in capillary pulmonary leakage, alveolar damage, and development of acute respiratory distress syndrome. Furthermore, SARS-CoV-2 can spread through pulmonary mechanoreceptors and chemoreceptors to medullary respiratory center in a retrograde manner resulting in sudden respiratory failure. Taken together, DSN in Covid-19 is developed due to sympathetic storm and inhibition of Parasympathetic nervous system-mediated anti-inflammatory effect with development of cytokine storm. Therefore, sympathetic and cytokine storms together with activation of Renin-Angiotensin-System are the chief final pathway involved in the development of DSN in Covid-19.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , COVID-19/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Síndrome da Liberação de Citocina , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Prospectivos
6.
Zhonghua Yi Xue Za Zhi ; 101(42): 3490-3494, 2021 Nov 16.
Artigo em Chinês | MEDLINE | ID: mdl-34775707

RESUMO

Objective: To validate the accuracy and consistency of a previously established prediction model for the occurrence of hyperkalemia in non-dialytic chronic kidney disease (CKD) patients. Methods: All patients diagnosed with CKD from Outpatient Department of Shanghai Changzheng Hospital during the 4th quarter of 2020 were recruited. Demographic data, clinical characteristics and prediction model-related parameters of the patients were collected and analyzed. Receiver operating characteristic (ROC) curve was drawn to evaluate the effectiveness of the model, and the specificity and sensitivity were calculated based on the cut-off value of 4 obtained from the previous model. The improved Hanley method was used to compare the area under the curve (AUC) between the previously established model and current validation dataset. The calibration curve was drawn to verify the model calibration degree. Results: A total of 434 patients diagnosed with non-dialytic CKD were enrolled, among whom 233 were males and 201 were females, with an average age of (55±16) years. According to the measured serum potassium values, the prevalence of hyperkalemia was 7.6%. And 33 patients were allocated to the hyperkalemia group and 401 patients were to the normal potassium group. There was no significant difference in age and sex between the two groups (both P>0.05). A combination of hyperkalemia and heart failure (27.3% vs 3.7%, P<0.001), diabetes (42.4% vs 19.7%, P=0.002), and acidosis (51.5% vs 7.0%, P<0.001) were more frequently in the hyperkalemia group, compared with the normal serum potassium group. Patients in the hyperkalemia group were more likely to have a past history of serum potassium ≥5.0 mmol/L (48.5% vs 2.5%, P<0.001). For the drugs that could increase serum potassium levels, there was a significant correlation between Chinese herbal medicine and the occurrence of hyperkalemia, while renin-angiotensin-aldosterone system inhibitor (RAASi) and potassium supplementation showed no significant difference between the two groups. The results of ROC curve analysis showed that the AUC was 0.914, with the sensitivity of 84.8% and the specificity of 79.8% with the cut-off value of 4. The difference of AUC between the previously established risk assessment model of hyperkalemia in patients with non-dialytic CKD and current validation dataset was not statistically significant (Z=1.924, P=0.054), indicating the good accuracy and consistency of the prediction model. In the calibration curve, when the predicted risk of patients was below 0.4 or above 0.6, the prediction effect of the model was better. Conclusion: The previously-constructed hyperkalemia prediction model in non-dialytic CKD patients had good accuracy and consistency, and could be used to evaluate the risk of hyperkalemia in all stages of non-dialytic CKD patients.


Assuntos
Hiperpotassemia , Insuficiência Renal Crônica , Adulto , Idoso , China , Feminino , Humanos , Hiperpotassemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Potássio , Sistema Renina-Angiotensina
7.
Medicine (Baltimore) ; 100(41): e27496, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731131

RESUMO

ABSTRACT: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of albuminuria has been under-investigated in patients with type 2 diabetes mellitus. Patients with type 2 diabetes and regular outpatient visits were recruited from the Puli Branch of the Taichung Veterans General Hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the albuminuria incidence. Univariable and multivariable Cox regression analysis were employed to explore the relation between uric acid and incident albuminuria. Uric acid cutoffs for incident albuminuria were determined with the receiver operator characteristic curve. We included 247 qualified subjects (mean age: 64.78 years old [standard deviation = 11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident albuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident albuminuria (adjusted hazard ratio = 2.39; 95% confidence interval: 1.53-3.75; P < .001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident albuminuria. Serum uric acid was associated with incident albuminuria among patients with type 2 diabetes.


Assuntos
Albuminúria/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Ácido Úrico/sangue , Idoso , Albuminúria/etiologia , Animais , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Feminino , Humanos , Hipertensão/complicações , Hiperuricemia/complicações , Incidência , Masculino , Camundongos , Microvasos/lesões , Pessoa de Meia-Idade , Modelos Animais , Insuficiência Renal/etiologia , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco , Taiwan/epidemiologia
8.
J Med Invest ; 68(3.4): 292-296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759147

RESUMO

Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients. J. Med. Invest. 68 : 292-296, August, 2021.


Assuntos
Enzima de Conversão de Angiotensina 2 , Glomerulonefrite por IGA , Biópsia , Criança , Glomerulonefrite por IGA/metabolismo , Humanos , Rim/metabolismo , Sistema Renina-Angiotensina
9.
ESC Heart Fail ; 8(2): 1717-1721, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34596976

RESUMO

AIMS: Concern has been raised that treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the expression of angiotensin-converting enzyme 2 (ACE2), which acts as the entry receptor for SARS-CoV-2, and lead to an increased risk of death from SARS-CoV-2. We aimed to address this concern by evaluating the in vivo relationship of treatment with ACE inhibitors and angiotensin receptor blockers (ARB) with circulating plasma concentrations of ACE2 in a large cohort of patients with established cardiovascular disease (n = 1864) or cardiovascular risk factors (n = 2144) but without a history of heart failure. METHODS AND RESULTS: Angiotensin-converting enzyme 2 was measured in 4008 patients (median age 68, 33% women, 31% on ACE-inhibitors, 31% on ARB) using the SOMAscan proteomic platform (SomaLogic Inc, Colorado, USA). Plasma concentration of ACE2 was comparable in 1250 patients on ACE inhibitors (mean 5.99) versus patients without ACE inhibitors (mean 5.98, P = 0.54). Similarly, plasma concentration of ACE2 was comparable in 1260 patients on ARB (mean 5.99) versus patients without ARB (mean 5.98, P = 0.50). Plasma concentration of ACE2 was comparable in 2474 patients on either ACE inhibitors or ARB (mean 5.99) versus patients without ACE inhibitors or ARB (mean 5.98, P = 0.31). Multivariable quantile regression model analysis confirmed the lack of association between treatment with ACE inhibitors or ARB and ACE2 concentrations. Body mass index showed the only positive association with ACE2 plasma concentration (effect 0.015, 95% confidence interval 0.002 to 0.028, P = 0.024). CONCLUSIONS: In a large cohort of patients with established cardiovascular disease or cardiovascular risk factors but without heart failure, ACE inhibitors and ARB were not associated with higher plasma concentrations of ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Feminino , Humanos , Masculino , Proteômica , Sistema Renina-Angiotensina , SARS-CoV-2
10.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638859

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the coronavirus disease of 2019 (COVID-19) pandemic, has affected and continues to affect millions of people across the world. Patients with essential arterial hypertension and renal complications are at particular risk of the fatal course of this infection. In our study, we have modeled the selected processes in a patient with essential hypertension and chronic kidney disease (CKD) suffering from COVID-19, emphasizing the function of the renin-angiotensin-aldosterone (RAA) system. The model has been built in the language of Petri nets theory. Using the systems approach, we have analyzed how COVID-19 may affect the studied organism, and we have checked whether the administration of selected anti-hypertensive drugs (angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs)) may impact the severity of the infection. Besides, we have assessed whether these drugs effectively lower blood pressure in the case of SARS-CoV-2 infection affecting essential hypertensive patients. Our research has shown that neither the ACEIs nor the ARBs worsens the course infection. However, when assessing the treatment of hypertension in the active SARS-CoV-2 infection, we have observed that ARBs might not effectively reduce blood pressure; they may even have the slightly opposite effect. On the other hand, we have confirmed the effectiveness of arterial hypertension treatment in patients receiving ACEIs. Moreover, we have found that the simultaneous use of ARBs and ACEIs averages the effects of taking both drugs, thus leading to only a slight decrease in blood pressure. We are a way from suggesting that ARBs in all hypertensive patients with COVID-19 are ineffective, but we have shown that research in this area should still be continued.


Assuntos
COVID-19/complicações , Hipertensão Essencial/complicações , Insuficiência Renal Crônica/complicações , COVID-19/metabolismo , COVID-19/fisiopatologia , Simulação por Computador , Hipertensão Essencial/metabolismo , Hipertensão Essencial/fisiopatologia , Humanos , Modelos Biológicos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-34603503

RESUMO

Introduction: The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people. Results: The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (p = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups. Conclusion: Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.


Assuntos
COVID-19/genética , Peptidil Dipeptidase A/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Sistema Renina-Angiotensina , Adulto Jovem
12.
Sci Rep ; 11(1): 19752, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611227

RESUMO

Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.


Assuntos
COVID-19/patologia , Suscetibilidade a Doenças , Síndrome Metabólica/patologia , Animais , Fatores de Coagulação Sanguínea/genética , Fatores de Coagulação Sanguínea/metabolismo , COVID-19/complicações , COVID-19/virologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dieta Hiperlipídica/veterinária , Modelos Animais de Doenças , Humanos , Imunidade Inata/genética , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/genética , Agregação Plaquetária , Receptores Purinérgicos P2Y1/genética , Receptores Purinérgicos P2Y1/metabolismo , Sistema Renina-Angiotensina , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Suínos , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
13.
Int J Biol Sci ; 17(14): 3795-3817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671200

RESUMO

Background: SARS-CoV-2, the cause of the worldwide COVID-19 pandemic, utilizes the mechanism of binding to ACE2 (a crucial component of the renin-angiotensin system [RAS]), subsequently mediating a secondary imbalance of the RAS family and leading to severe injury to the host. However, very few studies have been conducted to reveal the mechanism behind the effect of SARS-CoV-2 on tumors. Methods: Demographic data extracted from 33 cancer types and over 10,000 samples were employed to determine the comprehensive landscape of the RAS. Expression distribution, pretranscriptional and posttranscriptional regulation and posttranslational modifications (PTMs) as well as genomic alterations, DNA methylation and m6A modification were analyzed in both tissue and cell lines. The clinical phenotype, prognostic value and significance of the RAS during immune infiltration were identified. Results: Low expression of AGTR1 was common in tumors compared to normal tissues, while very low expression of AGTR2 and MAS1 was detected in both tissues and cell lines. Differential expression patterns of ACE in ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC) were correlated with ubiquitin modification involving E3 ligases. Genomic alterations of the RAS family were infrequent across TCGA pan-cancer program, and ACE had the highest alteration frequency compared with other members. Low expression of AGTR1 may result from hypermethylation in the promoter. Downregulation of RAS family was linked to higher clinical stage and worse survival (as measured by disease-specific survival [DSS], overall survival [OS] or progression-free interval [PFI]), especially for ACE2 and AGTR1 in KIRC. ACE-AGTR1, a classical axis of the RAS family related to immune infiltration, was positively correlated with M2-type macrophages, cancer-associated fibroblasts (CAFs) and immune checkpoint genes in most cancers. Conclusion: ACE, ACE2, AGT and AGTR1 were differentially expressed in 33 types of cancers. PTM of RAS family was found to rely on ubiquitination. ACE2 and AGTR1 might serve as independent prognostic factors for LGG and KIRC. SARS-CoV-2 might modify the tumor microenvironment by regulating the RAS family, thus affecting the biological processes of cancer.


Assuntos
Neoplasias/metabolismo , Sistema Renina-Angiotensina , SARS-CoV-2/metabolismo , COVID-19/complicações , COVID-19/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Neoplasias/etiologia , Neoplasias/mortalidade , Neoplasias/terapia , Processamento de Proteína Pós-Traducional
14.
Artigo em Russo | MEDLINE | ID: mdl-34714002

RESUMO

High neuroprotective activity of renin-angiotensin-aldosterone system (RAAS) inhibitors in patients with vascular diseases of the brain and spinal cord has been confirmed. OBJECTIVE: To evaluate the effect of renin-angiotensin-aldosterone system inhibitors on functional activity of the spinal cord and nerve roots in patients with degenerative lumbar spine diseases. MATERIAL AND METHODS: A retrospective observational cohort study was performed. We evaluated clinical and radiological parameters (gender, age of patients, type of antihypertensive drug, concomitant diseases, ODI (6) and SF-36 (7) scores of patient quality of life), functional recovery, increase of signal intensity and its area in T2WIs, localization and maximum spinal canal stenosis, as well as maximum spinal cord and nerve root compression. RESULTS: The study included 117 medical records of respondents (88 men and 29 women aged 56.9±13.2 years) who underwent lumbar spine surgery for degenerative diseases. Arterial hypertension was verified in 68 (58.1%) patients, diabetes mellitus in 22 (18.8%) respondents. Age (p=0.002), diabetes mellitus (p=0.007), arterial hypertension (p=0.015) and antihypertensive therapy (p=0.023) were significantly associated with worse clinical and neurological status of patients. Binary logistic regression model demonstrated that only arterial hypertension was significantly associated with low preoperative quality of life (p=0.002). CONCLUSION: Intake of AT II-1 receptor blockers and angiotensin converting enzyme inhibitors for arterial hypertension is a significant predictor of decrease in signal intensity of the spinal cord and its roots according to T2WIs.


Assuntos
Hipertensão , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Humanos , Masculino , Qualidade de Vida , Estudos Retrospectivos , Medula Espinal
15.
Internist (Berl) ; 62(11): 1153-1165, 2021 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-34605971

RESUMO

Heart failure and renal insufficiency as well as pulmonary hypertension are pathophysiologically closely associated as a cardio-renal or cardio-pulmonary-renal syndrome. Due to the frequent hospitalization of patients affected by this syndrome, it is of high medical and also health economic relevance. Besides the inhibition of the renin-angiotensin-aldosterone system (RAAS), multimodal treatment options are available with mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors and sodium-glucose transporter 2 (SGLT-2) inhibitors. Profound knowledge of the pathophysiology and the therapeutic options is as necessary for an optimized medical care as patient-oriented, transdisciplinary and cross-sectoral care.


Assuntos
Insuficiência Cardíaca , Insuficiência Renal , Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal/terapia , Sistema Renina-Angiotensina , Volume Sistólico
16.
J Infect Public Health ; 14(11): 1686-1692, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34649043

RESUMO

As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead to high blood pressure. Furthermore, SARS-CoV-2 infection seems to reduce the functional expression of ACE2. Given these circumstances, it might be advisable to consider a treatment plan for COVID-19 patients with CVD in an approach that would neither aggravate the vasodeleterious arm of the renin-angiotensinogen-aldosterone system (RAAS) nor compromise the vasoprotective arm of RAAS but is effective to minimize or if possible, inhibit the viral replication. Given the immune modulatory role of Zn in both CVD and COVID-19 pathogenesis, zinc supplement to the selective treatment plan for CVD and COVID-19 comorbid conditions, to be decided by the clinicians depending on the cardiovascular conditions of the patients, might greatly improve the therapeutic outcome. Notably, ACE2 is a zinc metalloenzyme and zinc is also known to inhibit viral replication.


Assuntos
COVID-19 , Doenças Cardiovasculares , Enzima de Conversão de Angiotensina 2 , Doenças Cardiovasculares/epidemiologia , Comorbidade , Humanos , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina , SARS-CoV-2 , Zinco
17.
Geroscience ; 43(5): 2289-2304, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34674152

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is essential for SARS-CoV-2 cellular entry. Here we studied the effects of common comorbidities in severe COVID-19 on ACE2 expression. ACE2 levels (by enzyme activity and ELISA measurements) were determined in human serum, heart and lung samples from patients with hypertension (n = 540), heart transplantation (289) and thoracic surgery (n = 49). Healthy individuals (n = 46) represented the controls. Serum ACE2 activity was increased in hypertensive subjects (132%) and substantially elevated in end-stage heart failure patients (689%) and showed a strong negative correlation with the left ventricular ejection fraction. Serum ACE2 activity was higher in male (147%), overweight (122%), obese (126%) and elderly (115%) hypertensive patients. Primary lung cancer resulted in higher circulating ACE2 activity, without affecting ACE2 levels in the surrounding lung tissue. Male sex resulted in elevated serum ACE2 activities in patients with heart transplantation or thoracic surgery (146% and 150%, respectively). Left ventricular (tissular) ACE2 activity was unaffected by sex and was lower in overweight (67%), obese (62%) and older (73%) patients with end-stage heart failure. There was no correlation between serum and tissular (left ventricular or lung) ACE2 activities. Neither serum nor tissue (left ventricle or lung) ACE2 levels were affected by RAS inhibitory medications. Abandoning of ACEi treatment (non-compliance) resulted in elevated blood pressure without effects on circulating ACE2 activities. ACE2 levels associate with the severity of cardiovascular diseases, suggestive for a role of ACE2 in the pathomechanisms of cardiovascular diseases and providing a potential explanation for the higher mortality of COVID-19 among cardiovascular patients. Abandoning RAS inhibitory medication worsens the cardiovascular status without affecting circulating or tissue ACE2 levels.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Enzima de Conversão de Angiotensina 2 , Biomarcadores , Humanos , Masculino , Sistema Renina-Angiotensina , Volume Sistólico , Função Ventricular Esquerda
18.
Med Clin North Am ; 105(6): 1065-1080, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688415

RESUMO

Hyperaldosteronism is a relatively more common disorder than previously recognized. Patients with hyperaldosteronism are at high risk for cardiovascular events. Patients suspected of having hyperaldosteronism should undergo initial screening and subsequent confirmatory testing to establish a biochemical diagnosis. Although adrenal computed tomography/magnetic resonance imaging scans often define a disease's subtype, adrenal vein sampling, in order to determine lateralization, may be necessary in some patients who are surgical candidates. Medical therapy using optimal doses of mineralocorticoid receptor antagonists can control symptoms and normalize plasma renin activity. The long-term outcome of patients treated with either surgical or optimal medical therapy appears similar.


Assuntos
Aldosterona/metabolismo , Hiperaldosteronismo/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Aldosterona/sangue , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Renina/metabolismo , Sistema Renina-Angiotensina/fisiologia
19.
Med Hypotheses ; 157: 110705, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34670172

RESUMO

Sedentary lifestyle increases the risk of hospitalization for COVID-19 independently of other factors. There is enough statistics to show that exercise prevents severe forms of COVID-19, but current recommendations do not set an upper limit for exercise intensity. The hypothesis presented in the paper states that intense exercise, through blood hypoxia, increases the expression of transmembrane angiotensin-converting enzyme 2 (tACE2) in the vascular endothelium, increasing the risk of developing serious forms of disease, especially in the untrained. On the other hand, moderate-intensity exercise increases the blood concentration of soluble angiotensin-converting enzyme 2 (ACE2) which has a protective role for SARS-CoV-2 infection and may prevent complications. The importance of this hypothesis consists in the revision of COVID-19 prophylaxis programs through physical exercises, with the possibility of administration of antioxidants to speed up the adaptation of vascular endothelial cells to exertion.


Assuntos
COVID-19 , Células Endoteliais , Endotélio Vascular/metabolismo , Exercício Físico , Humanos , Sistema Renina-Angiotensina , SARS-CoV-2
20.
Cells ; 10(10)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34685735

RESUMO

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.


Assuntos
COVID-19/sangue , COVID-19/metabolismo , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Humanos , Peptidil Dipeptidase A/metabolismo , Renina/farmacologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...