Hypertension最新文献

{"title":"Prevalence of Hyperkalemia and Familial Hyperkalemic Hypertension in 5100 Patients Referred to a Tertiary Hypertension Unit.","authors":"Martina Tetti, Jacopo Burrello, Marguerite Hureaux, Clarisse Billon, Eric Clauser, Franco Veglio, Franco Rabbia, Barbara Pasini, Annalisa Crisetti, Xavier Jeunemaitre, Paolo Mulatero, Silvia Monticone","doi":"10.1161/HYPERTENSIONAHA.124.23500","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23500","url":null,"abstract":"<p><strong>Background: </strong>Hyperkalemia is a frequent electrolyte alteration whose prevalence varies widely, depending on the adopted cutoff, the setting (inpatients versus outpatients), and the characteristics of the study population. Familial hyperkalemic hypertension (FHH) is a rare cause of hypertension, hyperkalemia, and hyperchloremic metabolic acidosis.</p><p><strong>Methods: </strong>In this retrospective observational study, we investigated the prevalence of hyperkalemia (serum K⁺ >5.2 mmol/L on 2 repeated measurements) in 5100 referred patients affected by arterial hypertension, the potential causes, and the associated cardiovascular risk profile.</p><p><strong>Results: </strong>Overall, 374 (7.3%) patients had hyperkalemia. This was associated with drugs known to increase K⁺ levels (74.6%), chronic kidney disease (33.7%), or both (24.3%). Among the 60 patients with unexplained hyperkalemia, 3 displayed a clinical and biochemical phenotype suggestive of FHH that was genetically confirmed in 2 of them (0.04% in the entire cohort). FHH prevalence rose to 3.3% in patients with unexplained hyperkalemia and up to 29% (2/7) if they had serum K⁺>5.8 mmol/L. The genetic cause of FHH was a missense variant affecting the acidic motif of <i>WNK1</i> in 1 family and a rare <i>CUL3</i> splicing variant, whose functional significance was confirmed by a minigene assay in another. Finally, we observed a significant association between hyperkalemia and the occurrence of cardiovascular events, metabolic syndrome, and organ damage, independent of potential confounding factors.</p><p><strong>Conclusions: </strong>The identification of hyperkalemia in patients with hypertensive has prognostic implications. A timely diagnosis of FHH is important for effective management of hypertension, electrolyte imbalance correction with tailored treatment, and genetic counseling.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use and Cost Patterns of Antihypertensive Medications in the United States From 1996 to 2021.","authors":"Joshua A Jacobs, Anthony Rodgers, Brandon K Bellows, Inmaculada Hernandez, Nelson Wang, Catherine G Derington, Jordan B King, Alexander R Zheutlin, Paul K Whelton, Brent M Egan, William C Cushman, Adam P Bress","doi":"10.1161/HYPERTENSIONAHA.124.23509","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23509","url":null,"abstract":"<p><strong>Background: </strong>Antihypertensive medication use patterns have likely been influenced by changing costs and accessibility over the past 3 decades. This study examines the relationships between patent exclusivity loss, medication costs, and national health policies on antihypertensive medication use.</p><p><strong>Methods: </strong>Using 1996 to 2021 Medical Expenditure Panel Survey data of US adults with hypertension taking at least 1 antihypertensive medication, we conducted a cross-sectional analysis. We explored the associations between patent exclusivity loss, per-pill costs, and Medicare Part D enactment on medication use over time, focusing on the most commonly used medications (lisinopril, amlodipine, losartan, hydrochlorothiazide, and metoprolol).</p><p><strong>Results: </strong>The unweighted sample comprised 50 095 US adults (mean age, 62 years; 53% female). The survey-weighted number of adults taking antihypertensive medications increased from 22 million (95% CIs, 20-23 million) to 55 million (95% CI, 51-60 million) between 1996 and 2021. Loss of patent exclusivity led to increased medication fills, notably for lisinopril, amlodipine, and losartan, which all exhibited within-class dominance. However, per-pill cost decreases coinciding with Medicare Part D did not increase the number of individuals treated or the use of specific antihypertensive medications or classes.</p><p><strong>Conclusions: </strong>The increase in antihypertensive medication use over the past decades highlights the significant impact of loss of patent exclusivity on the uptake in the use of specific medications. These findings underscore the complexity of factors influencing medication use, beyond cost reductions alone, and suggest that policies need to consider multiple facets to effectively improve antihypertensive medication accessibility and utilization.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Hypertension and Its Management Throughout Life.","authors":"Wan-Jin Yeo, Rahul Abraham, Aditya L Surapaneni, Pascal Schlosser, Shoshana Ballew, Bige Ozkan, Carina M Flaherty, Bing Yu, Joseph V Bonventre, Chirag Parikh, Paul L Kimmel, Ramachandran S Vasan, Josef Coresh, Morgan E Grams","doi":"10.1161/HYPERTENSIONAHA.124.22980","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.22980","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of hypertension and uncontrolled hypertension may differ by age and sex.</p><p><strong>Methods: </strong>We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models.</p><p><strong>Results: </strong>The prevalence of hypertension increased from 40% (ages, 43-46 years) to 93% (ages, 91-94 years). Within hypertensive individuals, the prevalence of uncontrolled hypertension was higher in men (33%) than women (23%) at ages 43 to 46 years but became higher in women than men starting at ages 61 to 64, with 56% of women and 40% men having uncontrolled hypertension at ages 91 to 94. This sex difference was not explained by differences in coronary heart disease, diabetes, body mass index, estimated glomerular filtration rate, number of antihypertension medications, classes of medications, or adherence to medications. In both sexes, uncontrolled hypertension was associated with a higher risk for chronic kidney disease progression (hazard ratio, 1.5 [1.2-1.9]; <i>P</i>=4.5×10^-⁴), heart failure (hazard ratio, 1.6 [1.4-2.0]; <i>P</i>=8.1×10^-⁷), stroke (hazard ratio, 2.1 [1.6-2.8]; <i>P</i>=1.8×10^-⁸), and mortality (hazard ratio, 1.5 [1.3-1.6]; <i>P</i>=6.2×10^-¹⁹).</p><p><strong>Conclusions: </strong>Sex differences in the prevalence of hypertension and uncontrolled hypertension vary by age, with the latter having implications for health throughout the life course.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Achieving Equity in Hypertension: A Review of Current Efforts by the American Heart Association.","authors":"Shakia T Hardy, Valy Fontil, Glenn H Dillon, Daichi Shimbo","doi":"10.1161/HYPERTENSIONAHA.124.20533","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.20533","url":null,"abstract":"<p><p>The purpose of this article is to summarize disparities in blood pressure (BP) by race in the United States, discuss evidence-based strategies to increase equity in BP, review recent American Heart Association BP equity initiatives, and highlight missed opportunities for achieving equity in hypertension. Over 122 million American adults have hypertension, with the highest prevalence among Black Americans. Racial disparities in hypertension and BP control in the United States are estimated to be the single largest contributor to the excess risk for cardiovascular disease among Black versus White adults. Worsening disparities in cardiovascular disease and life expectancy during the COVID-19 pandemic warrant an evaluation of the strategies and opportunities to increase equity in BP in the United States. Racial disparities in hypertension are largely driven by systemic inequities that limit access to quality education, economic opportunities, neighborhoods, and health care. To address these root causes, recent studies have evaluated evidence-based strategies, including community health workers, digital health interventions, team-based care, and mobile health care to enhance access to health education, screenings, and BP care in Black communities. In 2021, the American Heart Association made a $100 million pledge and 10 commitments to support health equity. This commitment included implementing multifaceted interventions with a focus on hypertension as a seminal risk factor contributing to disparities in cardiovascular disease mortality and morbidity. The American Heart Association is one organizational example of advocacy for equity in BP. Achieving equity nationwide will require sustained collaboration among individual stakeholders and public, private, and community organizations to address barriers across multiple socioecological levels.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Snoring and Daytime Sleepiness With Subsequent Incident Hypertension: A Population-Based Cohort Study.","authors":"Pauline Balagny, Emmanuelle Vidal-Petiot, Sofiane Kab, Justine Frija, Philippe Gabriel Steg, Marcel Goldberg, Marie Zins, Marie-Pia d'Ortho, Emmanuel Wiernik","doi":"10.1161/HYPERTENSIONAHA.124.23007","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.23007","url":null,"abstract":"<p><strong>Background: </strong>There is a strong association between obstructive sleep apnea and hypertension, but the effects of obstructive sleep apnea symptoms on the risk of incident hypertension are not well documented. The aim of this prospective study was to examine whether snoring and sleepiness are associated with incident hypertension.</p><p><strong>Methods: </strong>Data from the French population-based CONSTANCES cohort were analyzed. Normotensive participants, aged 18 to 69 years, were included between 2012 and 2016 and screened for snoring, morning fatigue, and daytime sleepiness in 2017 using items of the Berlin Questionnaire. We used Cox models, adjusted for multiple potential confounders, including body mass index, baseline blood pressure, sleep duration, and depressive symptoms, to compute hazards ratios of incidentally treated hypertension.</p><p><strong>Results: </strong>Among 34 727 subjects, the prevalence of self-reported habitual snoring, morning fatigue, and excessive daytime sleepiness (≥3× a week for each) was 23.6%, 16.6%, and 19.1%, respectively. During a median follow-up of 3.1 years (interquartile range, 3.0-3.5), the incidence of treated hypertension was 4.1%. The risk of de novo treated hypertension was higher in participants who reported habitual snoring (adjusted hazard ratio, 1.17 [95% CI, 1.03-1.32]) and excessive daytime sleepiness (adjusted hazard ratio, 1.42 [95% CI, 1.24-1.62]), and increased with the weekly frequency of symptoms, with a dose-dependent relationship (<i>P</i>_trend≤0.02 for all symptoms).</p><p><strong>Conclusions: </strong>Self-reported snoring and excessive daytime sleepiness are associated with an increased risk of developing hypertension. Identification of snoring and daytime sleepiness may be a useful public health screening tool in primary care for hypertension prevention.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.","authors":"Allan Kardec Nogueira de Alencar, Kenneth F Swan, Smruti Mahapatra, Sarah H Lindsey, Gabriella C Pridjian, Carolyn L Bayer","doi":"10.1161/HYPERTENSIONAHA.123.22303","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.123.22303","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia.</p><p><strong>Methods: </strong>To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1.</p><p><strong>Results: </strong>The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor.</p><p><strong>Conclusions: </strong>The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Metabolites Associated With Blood Pressure After Dietary Interventions.","authors":"Yixi Sun, Ruiyuan Zhang, Ling Tian, Yang Pan, Xiao Sun, Zhijie Huang, Jia Fan, Jing Chen, Kai Zhang, Shengxu Li, Wei Chen, Lydia A Bazzano, Tanika N Kelly, Jiang He, Joshua D Bundy, Changwei Li","doi":"10.1161/HYPERTENSIONAHA.124.22999","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22999","url":null,"abstract":"<p><strong>Background: </strong>The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions.</p><p><strong>Methods: </strong>In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP.</p><p><strong>Results: </strong>After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10^-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis.</p><p><strong>Conclusions: </strong>Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Apnea, Autonomic Disturbances, and Blood Pressure Variability.","authors":"Tomoyuki Tobushi, John S Floras","doi":"10.1161/HYPERTENSIONAHA.124.20433","DOIUrl":"10.1161/HYPERTENSIONAHA.124.20433","url":null,"abstract":"<p><p>Augmented blood pressure variability has emerged as a quantity predictive of adverse cardiovascular outcomes. Among the range of intrinsic and extrinsic factors shown to increase night-time, circadian, short-term, and long-term blood pressure variations, the presence and severity of obstructive sleep apnea have emerged as one of the most prevalent and potent. Obstructive sleep apnea alters acutely the normal nocturnal equilibrium between sympathetic and parasympathetic tone, magnifying nocturnal blood pressure oscillations, and induces sustained autonomic aftereffects with the capacity to amplify short-term and intersessional blood pressure variabilities. The object of this brief review is to synthesize the current understanding of the potential interrelations between obstructive sleep apnea, the acute and sustained autonomic disturbances that it elicits, and beat-to-beat blood pressure fluctuation during sleep, nocturnal dipping status, and day-to-day blood pressure variability and the consequences of these perturbations for cardiovascular risk.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive Kidney Failure by Angiotensinogen Inactivation in the Germline.","authors":"Florian J Wopperer, Eric Olinger, Antje Wiesener, Katharina A E Broeker, Karl X Knaup, Jan T Schaefer, Matthias Galiano, Karen Schneider, Mario Schiffer, Maike Büttner-Herold, André Reis, Roland Schmieder, Francesca Pasutto, Karl F Hilgers, Marko Poglitsch, Christine Ziegler, Robin Shoemaker, John A Sayer, Michael S Wiesener","doi":"10.1161/HYPERTENSIONAHA.124.22806","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22806","url":null,"abstract":"<p><strong>Background: </strong>Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms.</p><p><strong>Methods: </strong>Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project.</p><p><strong>Results: </strong>The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the <i>AGT</i> (angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated.</p><p><strong>Conclusions: </strong>Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with <i>AGT</i> mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic <i>AGT</i> silencing for the treatment of hypertension).</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.","authors":"Jason P Smith, Robert Paxton, Silvia Medrano, Nathan C Sheffield, Maria Luisa S Sequeira-Lopez, R Ariel Gomez","doi":"10.1161/HYPERTENSIONAHA.124.22886","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22886","url":null,"abstract":"<p><strong>Background: </strong>Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.</p><p><strong>Methods: </strong>We treated As4.1 cells (tumoral cells derived from mouse juxtaglomerular cells that constitutively express renin) with 3 inhibitors that target different factors required for renin transcription: H-89-dihydrochloride, PKA (protein kinase A) inhibitor; JQ1, Brd4 bromodomain inhibitor; and A-485, p300/CBP inhibitor. We performed assay for transposase-accessible chromatin with sequencing (ATAC-seq), single-cell RNA sequencing, cleavage under targets and tagmentation (CUT&Tag), and chromatin immunoprecipitation sequencing for H3K27ac (acetylation of lysine 27 of the histone H3 protein) and p300 binding on biological replicates of treated and control As4.1 cells.</p><p><strong>Results: </strong>In response to each inhibitor, <i>Ren1</i> expression was significantly reduced and reversible upon washout. Chromatin accessibility at the <i>Ren1</i> locus did not markedly change but was globally reduced at distal elements. Inhibition of PKA led to significant reductions in H3K27ac and p300 binding specifically within the <i>Ren1</i> super-enhancer region. Further, we identified enriched TF (transcription factor) motifs shared across each inhibitory treatment. Finally, we identified a set of 9 genes with putative roles across each of the 3 renin regulatory pathways and observed that each displayed differentially accessible chromatin, gene expression, H3K27ac, and p300 binding at their respective loci.</p><p><strong>Conclusions: </strong>Inhibition of renin expression in cells that constitutively synthesize and release renin is regulated by an epigenetic switch from an active to poised state associated with decreased cell-cell communication and an epithelial-mesenchymal transition. This work highlights and helps define the factors necessary for renin cells to alternate between myoendocrine and contractile phenotypes.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}