Journal of the renin-angiotensin-aldosterone system : JRAAS最新文献

{"title":"Empagliflozin Alleviates Left Ventricle Hypertrophy in High-Fat-Fed Mice by Modulating Renin Angiotensin Pathway.","authors":"Juliana Cordovil Cotrin, Gabriel Santos Martins de Souza, Tamiris Ingrid Petito-da-Silva, Luiz Eduardo Macedo Cardoso, Vanessa Souza-Mello, Sandra Barbosa-da-Silva","doi":"10.1155/2022/8861911","DOIUrl":"https://doi.org/10.1155/2022/8861911","url":null,"abstract":"Aims. The cardiobenefits of empagliflozin are multidimensional, and some mechanisms are still unclear. The aim of the present study was to evaluate the effect of treatment with empagliflozin on biometric parameters and gene expression in the local cardiac RAS, oxidative stress, and endoplasmic reticulum pathways in a mouse model. Main Methods. Forty male C57BL/6 mice were fed with control (C) or high-fat (HF) diets for 10 weeks. After that, the groups were redistributed according to the treatment with empagliflozin—CE or HFE. The empagliflozin was administered via food for 5 weeks (10 mg/kg/day). We performed biochemical analyses, blood pressure monitoring, oral glucose tolerance test, left ventricle (LV) stereology, RT-qPCR for genes related to classical and counterregulatory local RAS, oxidative stress, and endoplasmic reticulum stress. Key Findings. In comparison to HF, HFE decreased body mass and improved glucose intolerance and insulin resistance. The cardiac parameters were enhanced after treatment as expressed by decrease in plasma cholesterol, plasma uric acid, and systolic blood pressure. In addition, LV analysis showed that empagliflozin reduces cardiomyocyte area and LV thickness. The local RAS had less activity of the classical pathway and positive effects on the counterregulatory pathway. Empagliflozin treatment also decreased oxidative stress and endoplasmic reticulum stress-related genes. Significance. Our results suggests that empagliflozin modulates the local RAS pathway towards alleviation of oxidative stress and ER stress in the LV, which may be a route to its effects on improved cardiac remodeling.","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"8861911"},"PeriodicalIF":2.9,"publicationDate":"2022-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39882555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Mortality and Morbidity Related to Congestive Heart Failure with Reduced Ejection Fraction (CHFrEF) in Palestinian Patients Maintained on Submaximal Sacubitril/Valsartan Doses: A Pilot Study.","authors":"Raed Aqel,&nbsp;Tareq Z Alzughayyar,&nbsp;Sadi A Abukhalaf,&nbsp;Rami A Misk,&nbsp;Jihad Samer Zalloum","doi":"10.1155/2021/1829873","DOIUrl":"https://doi.org/10.1155/2021/1829873","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of sacubitril/valsartan, a newly introduced combination drug for heart failure with reduced ejection fraction (HFrEF), was demonstrated in the PARADIGM-HF trial conducted in Western countries. However, these findings need to be verified in the Middle Eastern context, where patients may exhibit a different response due to different environmental and racial factors.</p><p><strong>Objectives: </strong>The goal of this study was to evaluate the efficacy of submaximal sacubitril/valsartan doses in terms of improving the disease symptoms, as measured by the New York Heart Association (NYHA) classification and left ventricular ejection fraction (LVEF) percentage, as well as establish long-term morbidity and mortality associated with HFrEF among Palestinian patients administered target doses of an angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs). <i>Material and Methods</i>. This study involved a retrospective review of charts related to patients with HFrEF maintained on sacubitril/valsartan and was conducted in a referral cardiology clinic in Palestine. The inclusion criteria were age 18+, HFrEF diagnosis, sacubitril/valsartan usage for at least six months during the period between January 1, 2016, and June 30, 2019, and LVEF < 40%. The exclusion criteria included LVEF ≥ 40% and drug administration duration < 6 months. The collected data included NYHA class, as well as LVEF, serum sodium (Na), potassium (K), serum creatinine (Cr), and blood urea nitrogen (BUN) levels and the mortality rate before and after the minimum treatment duration. IBM SPSS STATISTICS for Windows, version 20.0, Armonk, NY: IBM Corp. IBM Corp., released 2012, was used for data analysis, whereby <i>T</i> score was calculated for comparisons between numerical groups, and <i>p</i> < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>The initial study sample comprised of 205 consecutive patients with HFrEF maintained on sacubitril/valsartan for at least six months from January 1, 2016, to June 30, 2019. Three patients were excluded due to attrition, along with further 12 patients with LVEF ≥ 40% (based on the PARADIGM-HF trial criteria). Throughout the treatment period, most patients showed escalating improvement in terms of the LVEF and NYHA classification, as LVEF = 29.8% and NYHA = 3 were obtained on average before initiating sacubitril/valsartan, compared to 41% and 1.7, respectively, after 6-month treatment (<i>p</i> = 0.0003 and 0.046, respectively). These improvements in LVEF and NYHA class were noted across all sacubitril/valsartan doses (50-400 mg). However, 23 patients (12%) died while undergoing sacubitril/valsartan treatment.</p><p><strong>Conclusion: </strong>A significant long-term reduction in the mortality and morbidity rates was observed in Palestinian patients with HFrEF maintained on submaximal doses of sacubitril/valsartan.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"1829873"},"PeriodicalIF":2.9,"publicationDate":"2021-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39819830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Endogenous Brain Renin-Angiotensin System and Drugs Acting on It.","authors":"Aswar Urmila,&nbsp;Patil Rashmi,&nbsp;Ghag Nilam,&nbsp;Bodhankar Subhash","doi":"10.1155/2021/9293553","DOIUrl":"https://doi.org/10.1155/2021/9293553","url":null,"abstract":"<p><p>The RAS (renin-angiotensin system) is the part of the endocrine system that plays a prime role in the control of essential hypertension. Since the discovery of brain RAS in the seventies, continuous efforts have been put by the scientific committee to explore it more. The brain has shown the presence of various components of brain RAS such as angiotensinogen (AGT), converting enzymes, angiotensin (Ang), and specific receptors (ATR). AGT acts as the precursor molecule for Ang peptides-I, II, III, and IV-while the enzymes such as prorenin, ACE, and aminopeptidases A and N synthesize it. AT1, AT2, AT4, and mitochondrial assembly receptor (MasR) are found to be plentiful in the brain. The brain RAS system exhibits pleiotropic properties such as neuroprotection and cognition along with regulation of blood pressure, CVS homeostasis, thirst and salt appetite, stress, depression, alcohol addiction, and pain modulation. The molecules acting through RAS predominantly ARBs and ACEI are found to be effective in various ongoing and completed clinical trials related to cognition, memory, Alzheimer's disease (AD), and pain. The review summarizes the recent advances in the brain RAS system highlighting its significance in pathophysiology and treatment of the central nervous system-related disorders.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"9293553"},"PeriodicalIF":2.9,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39739030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alamandine: Potential Protective Effects in SARS-CoV-2 Patients.","authors":"Ava Soltani Hekmat,&nbsp;Kazem Javanmardi","doi":"10.1155/2021/6824259","DOIUrl":"https://doi.org/10.1155/2021/6824259","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) can occur due to contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has no confined treatment and, consequently, has high hospitalization and mortality rates. Moreover, people who contract COVID-19 present systemic inflammatory spillover. It is now known that COVID-19 pathogenesis is linked to the renin-angiotensin system (RAS). COVID-19 invades host cells via the angiotensin-converting enzyme 2 (ACE2) receptor-as such, an individual's susceptibility to COVID-19 increases alongside the upregulation of this receptor. COVID-19 has also been associated with interstitial pulmonary fibrosis, which leads to acute respiratory distress, cardiomyopathy, and shock. These outcomes are thought to result from imbalances in angiotensin (Ang) II and Ang-(1-7)/alamandine activity. ACE2, Ang-(1-7), and alamandine have potent anti-inflammatory properties, and some SARS-CoV-2 patients exhibit high levels of ACE2 and Ang-(1-7). This phenomenon could indicate a failing physiological response to prevent or reduce the severity of inflammation-mediated pulmonary injuries. Alamandine, which is another protective component of the RAS, has several health benefits owing to its antithrombogenic, anti-inflammatory, and antifibrotic characteristics. Alamandine alleviates pulmonary fibrosis via the Mas-related G protein-coupled receptor D (MrgD). Thus, a better understanding of this pathway could uncover novel pharmacological strategies for altering proinflammatory environments within the body. Following such strategies could inhibit fibrosis after SARS-CoV-2 infection and, consequently, prevent COVID-19.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"6824259"},"PeriodicalIF":2.9,"publicationDate":"2021-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39683935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Level and Significance of Circulating Angiotensin-III in Patients with Coronary Atherosclerosis.","authors":"Guoqing Yao,&nbsp;Wenjing Li,&nbsp;Wenzhao Liu,&nbsp;Jingbo Xing,&nbsp;Cheng Zhang","doi":"10.1155/2021/1704762","DOIUrl":"https://doi.org/10.1155/2021/1704762","url":null,"abstract":"<p><strong>Objective: </strong>Angiotensin-III (Ang-III) is the downstream product of angiotensin-II (Ang-II) metabolized by aminopeptidase A (APA). At present, the research of Ang-III mainly concentrates on hypertension and the central renin-angiotensin system (RAS). However, few studies have focused on the relationship between Ang-III and coronary atherosclerosis (CAS).</p><p><strong>Methods and results: </strong>Plasma Ang-III and APA levels were measured by the enzyme-linked immunosorbent assay (ELISA) in 44 normal subjects and 84 patients confirmed as having CAS by coronary angiography. Circulating Ang-III levels were significantly lower in patients with CAS than in normal controls (<i>P</i> = 0.013). APA levels were slightly lower in the CAS group (<i>P</i> = 0.324). According to the severity of atherosclerosis, CAS patients were divided into two groups. Compared with the controls, the APA and Ang-III levels were lower in the high scoring group and APA decreased significantly.</p><p><strong>Conclusions: </strong>Circulating Ang-III levels were reduced in patients with CAS, and the possible reason may be related to the decrease in the APA level.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"1704762"},"PeriodicalIF":2.9,"publicationDate":"2021-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39482043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Ace D/I Polymorphism Could Affect the Clinicobiological Course of COVID-19.","authors":"Elifcan Aladag,&nbsp;Zahit Tas,&nbsp;Bilgesu Safak Ozdemir,&nbsp;Tayfun Hilmi Akbaba,&nbsp;Meltem Gulsun Akpınar,&nbsp;Hakan Goker,&nbsp;Tugce Unalan-Altintop,&nbsp;Ahmet Cagkan Inkaya,&nbsp;Alpaslan Alp,&nbsp;Gokhan Metan,&nbsp;Ibrahim Celalettin Haznedaroglu,&nbsp;Banu Balci-Peynircioglu,&nbsp;Nilgun Sayinalp","doi":"10.1155/2021/5509280","DOIUrl":"https://doi.org/10.1155/2021/5509280","url":null,"abstract":"<p><strong>Introduction: </strong>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. <i>Patients and Methods</i>. 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.</p><p><strong>Results: </strong>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, <i>p</i> < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (<i>p</i> = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"5509280"},"PeriodicalIF":2.9,"publicationDate":"2021-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39482044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Losartan and Eprosartan Induce a Similar Effect on the Acute Rise in Serum Uric Acid Concentration after an Oral Fructose Load in Patients with Metabolic Syndrome.","authors":"Anna Masajtis-Zagajewska,&nbsp;Jacek Majer,&nbsp;Michał Nowicki","doi":"10.1155/2021/2214978","DOIUrl":"https://doi.org/10.1155/2021/2214978","url":null,"abstract":"<p><strong>Introduction: </strong>Excessive intake of fructose increases serum uric acid concentration. Hyperuricemia induces a negative effect on atherosclerosis and inflammation. Hyperuricemia is common in patients with arterial hypertension. Several antihypertensive drugs including diuretics increase serum uric acid concentration. In contrast, the angiotensin II receptor antagonist (ARB) losartan was found to lower serum uric acid though it may increase renal excretion while other ARBs showed mostly a neutral effect. In this study, effects of two AT1 receptor antagonists losartan and eprosartan on serum uric acid changes induced by oral fructose load were directly compared.</p><p><strong>Methods: </strong>The randomized, crossover, head-to-head comparative study comprised 16 ambulatory patients (mean age 64.5 ± 9.8 years). The patients fulfilled AHA/NHLBI 2005 criteria of metabolic syndrome. A daily single morning dose of each study drug (50 mg of losartan or 600 mg of eprosartan) was given during two 3-month periods in a random order separated by 2-week washout time. The oral fructose tolerance test (OFTT) was performed at baseline and after each two 3-onth treatment periods. Before and during OFTT, urine excretion of uric acid and creatinine was assessed in the first morning portion of urine. Blood samples for the measurement of serum uric acid and lipids were taken at baseline and 30, 60, and 120 minutes after oral intake of 75 g of fructose.</p><p><strong>Results: </strong>After 3-month treatment with eprosartan and losartan, both systolic and diastolic blood pressure decreased significantly and to a similar extent. After the treatment, serum uric acid and its baseline and postfructose urine excretion were unchanged. No significant changes of plasma lipids before and after OFTT were observed throughout the study.</p><p><strong>Conclusions: </strong>The study showed that in patients with hypertension and metabolic syndrome, both losartan and eprosartan have a neutral effect on fasting and postfructose load serum uric acid concentration and its urinary excretion. This trial is registered with NCT04954560.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"2214978"},"PeriodicalIF":2.9,"publicationDate":"2021-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39419936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin Receptor Blocker and Neprilysin Inhibitor Suppresses Cardiac Dysfunction by Accelerating Myocardial Angiogenesis in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet.","authors":"Yasunori Suematsu,&nbsp;Kohei Tashiro,&nbsp;Hidetaka Morita,&nbsp;Akihito Ideishi,&nbsp;Takashi Kuwano,&nbsp;Shin-Ichiro Miura","doi":"10.1155/2021/9916789","DOIUrl":"https://doi.org/10.1155/2021/9916789","url":null,"abstract":"<p><strong>Materials and methods: </strong>Male apolipoprotein E-knockout mice fed a high-fat diet were divided into control (CTL), valsartan (30 mg/kg) (VAL), sacubitril (30 mg/kg) (SAC), and valsartan plus sacubitril (30 mg/kg each) (VAL/SAC) groups after 4 weeks of prefeeding and were subsequently treated for 12 weeks.</p><p><strong>Results: </strong>The VAL/SAC group exhibited significantly higher serum brain natriuretic peptide levels; more subtle changes in left ventricular systolic diameter, fractional shortening, and ejection fraction, and significantly higher expression levels of natriuretic peptide precursor B and markers of angiogenesis, including clusters of differentiation 34, vascular endothelial growth factor A, and monocyte chemotactic protein 1, than the CTL group.</p><p><strong>Conclusions: </strong>Valsartan plus sacubitril preserved left ventricular systolic function in apolipoprotein E-knockout mice fed a high-fat diet. This result suggests that myocardial angiogenic factors induced by ARNI might provide cardioprotective effects.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"9916789"},"PeriodicalIF":2.9,"publicationDate":"2021-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39312705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine Reshapes the Balance of the Local Renin-Angiotensin System by Modulating Autophagy under Metabolic Stress in Pancreatic Islets.","authors":"Chenghu Huang,&nbsp;Pan Lei,&nbsp;Caibi Peng,&nbsp;Min Li,&nbsp;Yifei Guo,&nbsp;Xuefeng Li","doi":"10.1155/2021/9928986","DOIUrl":"https://doi.org/10.1155/2021/9928986","url":null,"abstract":"<p><strong>Results: </strong>Prolonged exposure to palmitate increased the expression of ACE and AngII type 1 receptor (ATR1) and decreased the ACE2 expression, which was partly offset by berberine. In ob/ob mice, berberine increased in tolerance to glucose, improved abnormal <i>β</i>-cell and <i>α</i>-cell distributions, upregulated ACE2 expression, and decreased autophagosomes and the expression of LC3 and SQSTM1/p62. Autophagosomes and expression of LC3 and SQSTM1/p62 were increased in ACE2KO mice.</p><p><strong>Conclusions: </strong>We demonstrated that berberine may improve the pancreatic islet function by regulating local RAS-mediated autophagy under metabolic stress.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"9928986"},"PeriodicalIF":2.9,"publicationDate":"2021-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39312706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the Na⁺/H⁺ Ion Exchanger on Susceptibility to COVID-19 and the Course of the Disease.","authors":"Medine Cumhur Cure,&nbsp;Erkan Cure","doi":"10.1155/2021/4754440","DOIUrl":"https://doi.org/10.1155/2021/4754440","url":null,"abstract":"<p><p>The Na⁺/H⁺ ion exchanger (NHE) pumps Na⁺ inward the cell and H⁺ ion outside the cell. NHE activity increases in response to a decrease in intracellular pH, and it maintains intracellular pH in a narrow range. Patients with obesity, diabetes, and hypertension and the elderly are prone to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The angiotensin II (Ang II) level is high in chronic diseases such as diabetes, hypertension, and obesity. Ang II is the main stimulator of NHE, and an increased Ang II level causes prolonged NHE activation in these patients. The long-term increase in NHE activity causes H⁺ ions to leave the cell in patients with diabetes, hypertension, and obesity. Increasing H⁺ ions outside the cell lead to an increase in oxidative stress and reactive oxygen species. H⁺ ion flows into the cell due to the increased oxidative stress. This vicious circle causes intracellular pH to drop. Although NHE is activated when intracellular pH decreases, there is prolonged NHE activation in chronic diseases such as aforementioned. Novel coronavirus disease 2019 (COVID-19) progression may be more severe and mortal in these patients. SARS-CoV-2 readily invades the cell at low intracellular pH and causes infection. The renin-angiotensin system and NHE play a vital role in regulating intracellular pH. The reduction of NHE activity or its prolonged activation may cause susceptibility to SARS-CoV-2 infection by lowering intracellular pH in patients with diabetes, hypertension, and obesity. Prolonged NHE activation in these patients with COVID-19 may worsen the course of the disease. Scientists continue to investigate the mechanism of the disease and the factors that affect its clinical progression.</p>","PeriodicalId":520698,"journal":{"name":"Journal of the renin-angiotensin-aldosterone system : JRAAS","volume":" ","pages":"4754440"},"PeriodicalIF":2.9,"publicationDate":"2021-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39204479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}