MicroRNAs Regulating Renin-Angiotensin-Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension.
Ontology highlight
ABSTRACT:
SUBMITTER: Improta-Caria AC
PROVIDER: S-EPMC8698399 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
MicroRNAs Regulating Renin-Angiotensin-Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension.
Improta-Caria Alex Cleber AC Aras Marcela Gordilho MG Nascimento Luca L De Sousa Ricardo Augusto Leoni RAL Aras-Júnior Roque R Souza Bruno Solano de Freitas BSF
Biomolecules 20211126 12
MicroRNAs are small non-coding RNAs that regulate gene and protein expression. MicroRNAs also regulate several cellular processes such as proliferation, differentiation, cell cycle, apoptosis, among others. In this context, they play important roles in the human body and in the pathogenesis of diseases such as cancer, diabetes, obesity and hypertension. In hypertension, microRNAs act on the renin-angiotensin-aldosterone system, sympathetic nervous system and left ventricular hypertrophy, however ...[more]
Similar Datasets
Project description:RationalePatients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up-regulated, but this may have long-term negative effects on the progression of iPAH.ObjectivesAssess systemic and pulmonary RAAS activity in patients with iPAH and determine the efficacy of chronic RAAS inhibition in experimental PAH.MethodsWe collected 79 blood samples from 58 patients with iPAH in the VU University Medical Center Amsterdam (between 2004 and 2010) to determine systemic RAAS activity.Measurements and main resultsWe observed increased levels of renin, angiotensin (Ang)I, and AngII, which were associated with disease progression (P < 0.05) and mortality (P < 0.05). To determine pulmonary RAAS activity, lung specimens were obtained from patients with iPAH (during lung transplantation, n = 13) and control subjects (during lobectomy or pneumonectomy for cancer, n = 14). Local RAAS activity in pulmonary arteries of patients with iPAH was increased, demonstrated by elevated angiotensin-converting enzyme activity in pulmonary endothelial cells and increased AngII type 1 (AT(1)) receptor expression and signaling. In addition, local RAAS up-regulation was associated with increased pulmonary artery smooth muscle cell proliferation via enhanced AT(1) receptor signaling in patients with iPAH compared with control subjects. Finally, to determine the therapeutic potential of RAAS activity, we assessed the chronic effects of an AT(1) receptor antagonist (losartan) in the monocrotaline PAH rat model (60 mg/kg). Losartan delayed disease progression, decreased right ventricular afterload and pulmonary vascular remodeling, and restored right ventricular-arterial coupling in rats with PAH.ConclusionsSystemic and pulmonary RAAS activities are increased in patients with iPAH and are associated with increased pulmonary vascular remodeling. Chronic inhibition of RAAS by losartan is beneficial in experimental PAH.
| S-EPMC5104838 | biostudies-literature
Project description:Chronic activation of the renin-angiotensin-aldosterone system (RAAS) promotes and perpetuates the syndromes of congestive heart failure, systemic hypertension, and chronic kidney disease. Excessive circulating and tissue angiotensin II (AngII) and aldosterone levels lead to a pro-fibrotic, -inflammatory, and -hypertrophic milieu that causes remodeling and dysfunction in cardiovascular and renal tissues. Understanding of the role of the RAAS in this abnormal pathologic remodeling has grown over the past few decades and numerous medical therapies aimed at suppressing the RAAS have been developed. Despite this, morbidity from these diseases remains high. Continued investigation into the complexities of the RAAS should help clinicians modulate (suppress or enhance) components of this system and improve quality of life and survival. This review focuses on updates in our understanding of the RAAS and the pathophysiology of AngII and aldosterone excess, reviewing what is known about its suppression in cardiovascular and renal diseases, especially in the cat and dog.
| S-EPMC6430926 | biostudies-literature
Project description:With the multiplication of COVID-19 severe acute respiratory syndrome cases due to SARS-COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. ACEis do not inhibit ACE2. Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as advocated by many medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.
| S-EPMC7172808 | biostudies-literature
Project description:The renin-angiotensin-aldosterone system (RAAS) is not the sole, but perhaps the most important volume regulator in vertebrates. To gain insights into the function and evolution of its components, we conducted a phylogenetic analysis of its main related genes. We found that important parts of the system began to appear with primitive chordates and tunicates and that all major components were present at the divergence of bony fish, with the exception of the Mas receptor. The Mas receptor first appears after the bony-fish/tetrapod divergence. This phase of evolutionary innovation happened about 400 million years ago. We found solid evidence that angiotensinogen made its appearance in cartilage fish. The presence of several RAAS genes in organisms that lack all the components shows that these genes have had other ancestral functions outside of their current role. Our analysis underscores the utility of sequence comparisons in the study of evolution. Such analyses may provide new hypotheses as to how and why in today's population an increased activity of the RAAS frequently leads to faulty salt and volume regulation, hypertension, and cardiovascular diseases, opening up new and clinically important research areas for evolutionary medicine.
| S-EPMC3354321 | biostudies-literature
Project description:The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis, is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, seem to be examples of RAAS-related arrhythmias because treatment with RAAS modulators, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest that RAAS has proarrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented.
| S-EPMC2600881 | biostudies-literature
Project description:Fibroblast growth factor 23 (FGF23) is elevated in patients with chronic kidney disease and contributes to left ventricular hypertrophy (LVH). The aim of the analysis was to determine whether this effect is mediated by the renin-angiotensin-aldosterone system (RAAS) in hemodialysis. Serum samples from 62 randomized hemodialysis patients with LVH were analyzed for plasma renin activity (PRA-S), angiotensin II (AngII), and metabolites, angiotensin-converting enzyme-2 (ACE2) and aldosterone using a high throughput mass spectrometry assay. Compared to healthy individuals, levels of the RAAS parameters PRA-S, AngII and aldosterone were generally lower [median (IQR) PRA-S 130 (46-269) vs. 196 (98, 238) pmol/L; AngII 70 (28-157) vs. 137 (76, 201) pmol/L; Aldosterone 130 (54, 278) vs. 196 (98, 238) pmol/L]. We did not find an indication that the effect of FGF23 on LVH was mediated by RAAS parameters, with all estimated indirect effects virtually zero. Furthermore, FGF23 was not associated with RAAS parameter levels throughout the study. While there was a clear association between FGF23 levels and left ventricular mass index (LVMI) at the end of the study and in the FGF23 fold change and LVMI change analysis, no association between RAAS and LVMI was observed. Serum concentrations of PRA-S, AngII, and aldosterone were below the ranges measured in healthy controls suggesting that RAAS is not systemically activated in hemodialysis patients. The effect of FGF23 on LVMI was not mediated by systemic RAAS activity. These findings challenge the current paradigm of LVH progression and treatment with RAAS blockers in dialysis.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT03182699], identifier [NCT03182699].
| S-EPMC9086596 | biostudies-literature
Project description:Because adult podocytes cannot proliferate and are therefore unable to self-renew, replacement of these cells depends on stem/progenitor cells. Although podocyte number is higher after renin-angiotensin-aldosterone system (RAAS) inhibition in glomerular diseases, the events explaining this increase are unclear. Cells of renin lineage (CoRL) have marked plasticity, including the ability to acquire a podocyte phenotype. To test the hypothesis that RAAS inhibition partially replenishes adult podocytes by increasing CoRL number, migration, and/or transdifferentiation, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R CoRL reporter mice to induce permanent labeling of CoRL with red fluorescent protein variant tdTomato. We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody. RAAS inhibition by enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin-receptor blocker) in FSGS mice stimulated the proliferation of CoRL, increasing the reservoir of these cells in the juxtaglomerular compartment (JGC). Compared with water or hydralazine, RAAS inhibition significantly increased the migration of CoRL from the JGC to the intraglomerular compartment (IGC), with more glomeruli containing RFP+CoRL and, within these glomeruli, more RFP+CoRL. Moreover, RAAS inhibition in FSGS mice increased RFP+CoRL transdifferentiation in the IGC to phenotypes, consistent with those of podocytes (coexpression of synaptopodin and Wilms tumor protein), parietal epithelial cells (PAX 8), and mesangial cells (α8 integrin). These results show that in the context of podocyte depletion in FSGS, RAAS inhibition augments CoRL proliferation and plasticity toward three different glomerular cell lineages.
| S-EPMC5118476 | biostudies-literature
Project description:BackgroundLeft ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. The decreased cardiac output over time leads to activation of the renin-angiotensin-aldosterone system which results in vasoconstriction by influencing salt-water homeostasis. Therefore, the purpose of the present study was to explore the association of single nucleotide polymorphisms (SNPs) in angiotensin I converting enzyme; ACE (rs4340), angiotensin II type1 receptor; AT1 (rs5186) and aldosterone synthase; CYP11B2 (rs1799998) with LVD.Methods and resultsThe present study was carried out in two cohorts. The primary cohort included 308 consecutive patients with angiographically confirmed CAD and 234 healthy controls. Among CAD, 94 with compromised left ventricle ejection fraction (LVEF ⩽ 45) were categorized as LVD. The ACE I/D, AT1 A1166C and CYP11B2 T-344C polymorphisms were determined by PCR. Our results showed that ACE I/D was significantly associated with CAD but not with LVD. However, AT1 1166C variant was significantly associated with LVD (LVEF ⩽ 45) (p value=0.013; OR=3.69), but CYP11B2 (rs1799998) was not associated with either CAD or LVD. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.020; OR=5.20).ConclusionAT1 A1166C plays important role in conferring susceptibility of LVD.
| S-EPMC3826383 | biostudies-literature
Project description:BackgroundWe investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle.Methods and resultsSingle ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those with <2 homozygous risk genotypes (low risk) at 2 time points: before the superior cavopulmonary connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (P<0.05), but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline, and height remained lower in the high-risk group at 14 months, especially in those receiving enalapril (P<0.05).ConclusionsRenin-angiotensin-aldosterone system-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact.Clinical trial registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT00113087.
| S-EPMC3137902 | biostudies-literature
Project description:AimsThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the ACE2 component of the renin-angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS-CoV-2 infection, therapeutic approaches, and clinical trials in this field.MethodsWe surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS-CoV-2 infection along with various COVID-19 therapies based on the RASS components were included in the study.ResultsACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang-(1-7) levels, which can be suggestive for their role as therapeutics against SARS-CoV-2 infection. Beta-adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID-19. Some antihyperglycemic agents could be potentially protective against COVID-19-induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID-19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies.ConclusionRegarding the suggested potential therapies for COVID-19, there are many clinical trials whose results might change the treatment strategies of SARS-CoV-2 infection. So, the results of well-organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID-19 will be useful in the management and therapy of the disease.
| S-EPMC8596942 | biostudies-literature