Hypertension最新文献

{"title":"Does Aspirin Affect Extracellular Vesicles Involved in the Pathogenesis of Preeclampsia? A Systematic Review and Meta-Analysis.","authors":"Angel Nilesh D'Crus, Soumyalekshmi Nair, Jessica Jellins, Fabricio Da Silva Costa, Jon Hyett, Carlos Salomon","doi":"10.1161/HYPERTENSIONAHA.125.24826","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.24826","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a challenging pregnancy disorder to treat, and current preventive measures are not always effective. Aspirin is prescribed as a preventive agent for pregnant women who are at high risk of developing preeclampsia although there is no definitive conclusion for its mechanism of action or efficacy. Extracellular vesicles (EVs) provide a picture of the physiological state of the cells from which they originate and have been implicated in both normal and pathological pregnancies. This study reviewed the potential effects of aspirin on EVs when prescribed for prevention of preeclampsia.</p><p><strong>Methods: </strong>The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to identify published studies from the CENTRAL, The Cochrane Library (Cochrane Central Register of Controlled Trials), MEDLINE on PubMed, CINAHL, Web of Science, and Embase from inception to March 2024.</p><p><strong>Results: </strong>Sixty-three studies met the inclusion criteria and were grouped as studies on aspirin-mediated prevention of preeclampsia (n=31), studies on EVs in the pathogenesis of preeclampsia (n=28), and studies on the effects of aspirin on EVs in preeclampsia (n=4). Meta-analysis of randomized control trials showed that the odds of preeclampsia occurrence is 36% less likely in the aspirin treatment group (odds ratio, 0.64 [95% CI, 0.47-0.87]; <i>P</i><0.01). EVs are involved in the pathogenesis of preeclampsia, and aspirin effectively reduced the negative effects of EVs in both in vitro and in vivo studies.</p><p><strong>Conclusions: </strong>Aspirin has an inhibitory effect on EVs in preeclampsia. However, further studies are needed to understand and confirm the mechanisms involved.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198889","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":"L-Citrulline Improves IGF-1 Signaling Pathway in Preeclampsia via Polyamines.","authors":"Andy W C Man, Joscha Steetskamp, Josche van der Ven, Gisela Reifenberg, Annette Hasenburg, Andreas Daiber, Ning Xia, Huige Li","doi":"10.1161/HYPERTENSIONAHA.125.24785","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.24785","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a severe pregnancy complication with no effective pharmacological therapy available. We previously demonstrated that L-citrulline supplementation improves preeclampsia phenotypes in Dahl salt-sensitive rats, an animal model of imposed preeclampsia. This study aimed to investigate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>Pregnant Dahl salt-sensitive rats were treated with L-citrulline. In addition, patients with preeclampsia were recruited to donate placenta and serum samples.</p><p><strong>Results: </strong>In patients with preeclampsia, the placental IGF-1 (insulin-like growth factor 1) expression was significantly reduced compared with healthy pregnancy, associated with a downregulation of ZEB1 (zinc finger E-box binding homeobox 1) and an upregulation of miR-486-5p and miR-210. L-citrulline supplementation in preeclampsia rats significantly increased the placental expression of IGF-1 and ZEB1 and reduced the expression of miR-486-5p and miR-210. Total serum polyamine level was reduced in patients with preeclampsia and pregnant Dahl salt-sensitive rats, while L-citrulline treatment maintained the serum polyamine level in Dahl salt-sensitive rats during pregnancy. Placental IGF-1 expression was positively correlated to serum polyamine levels. Moreover, both L-citrulline and polyamines normalized the expression of IGF-1 and some antiangiogenic markers in cultured human placental vascular endothelial cells treated with preeclampsia serum. Results from IGF-1 siRNA experiments indicate that part of the L-citrulline effects on gene expression was dependent on IGF-1.</p><p><strong>Conclusions: </strong>L-citrulline supplementation improves the IGF-1 signaling pathway in preeclampsia, at least partly, via polyamine production. Maternal supplementation with L-citrulline or polyamine may represent a safe and effective therapeutic strategy for preeclampsia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198890","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":"The Morbidity of Pediatric Hypertension.","authors":"Cynthia S Bell, Samuel S Gidding","doi":"10.1161/HYPERTENSIONAHA.124.24299","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.24299","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"82 6","pages":"1002-1003"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077602","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":"Hypertension Prevention and Healthy Life Expectancy in Black Adults: The Jackson Heart Study.","authors":"Kathryn Foti, Yiyi Zhang, Susan E Hennessy, Lisandro D Colantonio, Lama Ghazi, Shakia T Hardy, Milla E Arabadjian, Rushelle L Byfield, Valy Fontil, Cora E Lewis, Daichi Shimbo, Paul Muntner, Brandon K Bellows","doi":"10.1161/HYPERTENSIONAHA.124.23702","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23702","url":null,"abstract":"<p><strong>Background: </strong>The impact of preventing hypertension and maintaining normal blood pressure (BP) on life expectancy and healthy life expectancy (HLE) among Black adults, who are disproportionately affected by hypertension, has not been quantified.</p><p><strong>Methods: </strong>We used a discrete event simulation to estimate life expectancy and HLE among a cohort of Black adults from the Jackson Heart Study (n=4933) from age 20 to 100 years or until death. We modeled preventing hypertension as having BP <130/80 mm Hg and maintaining normal BP as having BP <120/80 mm Hg across the lifespan. In the primary analysis, we assumed that lowering BP decreased the risk of cardiovascular disease events, resulting in life expectancy and HLE gains. In a secondary analysis, we assumed that preventing hypertension and maintaining normal BP directly reduced both cardiovascular disease and mortality risk.</p><p><strong>Results: </strong>At age 20 years, the projected average life expectancy was age 80.8 (95% uncertainty interval [UI], 80.6-81.1) years, and HLE was 70.5 (95% UI, 70.3-70.7) healthy life years. In the primary analysis, preventing hypertension and maintaining normal BP added 0.9 (95% UI, 0.8-1.1) and 1.1 (95% UI, 0.9-1.3) years to life expectancy, respectively, and 2.7 (95% UI, 2.6-2.9) and 2.9 (95% UI, 2.7-3.1) healthy life years to HLE, respectively. In the secondary analysis, preventing hypertension and maintaining normal BP added 4.5 (95% UI, 4.3-4.6) and 4.6 (95% UI, 4.4-4.8) years to life expectancy, respectively, and 5.7 (95% UI, 5.6-5.8) and 5.9 (95% UI, 5.7-6.0) healthy life years to HLE, respectively.</p><p><strong>Conclusions: </strong>Preventing hypertension and maintaining normal BP were projected to increase life expectancy and HLE among Black adults.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1095-1105"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500324","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":"Blood Pressure-Elevating and Antihypertensive Medication Prescription Trends.","authors":"Ashutosh Kumar, Nicole L Therrien, John I Ogwuegbu, Jun Soo Lee, Hilary K Wall, John M Flack, Sandra L Jackson","doi":"10.1161/HYPERTENSIONAHA.124.24316","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24316","url":null,"abstract":"<p><strong>Background: </strong>Many medications can have blood pressure (BP)-elevating effects, which might negatively impact BP control among people with hypertension. This study examines trends in prescription fills for BP-elevating and antihypertensive medications, individually and concurrently, among US individuals.</p><p><strong>Methods: </strong>Quarterly trends of individual and concurrent fills for BP-elevating and antihypertensive medications were reported using the nationwide sample from IQVIA's Total Patient Tracker database, covering 94% of all retail prescription fills in the United States. We identified 1387 products containing BP-elevating medications and 240 products containing antihypertensive medications. Percentage change from Q1/2017 and average quarterly percent change from the joinpoint regression were used to present trends overall and by sex and age group (0-17, 18-44, 45-64, 65-74, and ≥75 years).</p><p><strong>Results: </strong>From 2017 to 2023, fills remained stable for BP-elevating medications alone and increased for antihypertensive medications alone (9.5% increase; from 10.1% to 11.0%; <i>P</i><0.001). Concurrent fills for antihypertensive and BP-elevating medications increased by 15.9% (from 5.4% to 6.2%; <i>P</i><0.001). Fills for BP-elevating medications were higher among adult women compared with men; among women aged 18 to 44 years, this was primarily due to the use of combined oral contraceptives. In Q4/2023, fills for BP-elevating medications were most common among those aged 65 to 74 years (women=30.7%; men=20.4%).</p><p><strong>Conclusions: </strong>These results provide the first nationwide trends in concurrent prescription fills for BP-elevating and antihypertensive medications, indicating an increasing trend. Our findings might inform clinician decision-making regarding medication selection for patients with hypertension.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1106-1115"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018409","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":"Youth Blood Pressure and Target Organ Injury Markers: The SHIP AHOY Study.","authors":"Gilad Hamdani, Elaine M Urbina, Stephen R Daniels, Bonita E Falkner, Michael A Ferguson, Joseph T Flynn, Coral D Hanevold, Julie R Ingelfinger, Philip R Khoury, Marc B Lande, Kevin E Meyers, Joshua Samuels, Mark Mitsnefes","doi":"10.1161/HYPERTENSIONAHA.124.23018","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23018","url":null,"abstract":"<p><strong>Background: </strong>Hypertension in adolescence is associated with subclinical target organ injury. We aimed to determine whether different blood pressure thresholds were associated with an increasing number of target organ injury markers in healthy adolescents.</p><p><strong>Methods: </strong>A total of 244 participants (mean age 15.5±1.8 years, 60.1% male adolescents) were studied. Participants were divided based on systolic clinic and systolic awake ambulatory blood pressure into low- (<75th percentile), mid- (75th-90th percentile), and high-risk (>90th percentile) groups. The ambulatory blood pressure phenotype was classified as normotensive, white-coat, masked, or sustained hypertension. Target organ injury assessments included left ventricular mass, systolic and diastolic function, and vascular stiffness. A multivariable general linear model was constructed to evaluate the association of different participant characteristics with higher numbers of target organ injury markers.</p><p><strong>Results: </strong>A total of 31.2% of participants had 1, 11.9% 2, 3.7% 3, and 0.8% 4 target organ injury markers. The number of target organ injury markers increased according to the risk groups: the percentage of participants with >1 marker in the low-, mid-, and high-risk groups was 6.7%, 19.1%, and 21.8% (<i>P</i>=0.02) and 9.6%, 15.8%, and 32.2% (<i>P</i><0.001), based on clinic and ambulatory blood pressure, respectively. Participants with white-coat (23%), masked (35%), and sustained hypertension (32%) were more likely to have >1 target organ injury marker than normotensives (8%, <i>P</i><0.001). The results were unchanged in multivariate analysis.</p><p><strong>Conclusions: </strong>High clinic and ambulatory blood pressure values, as well as ambulatory blood pressure phenotypes (white-coat, masked, and sustained hypertension), were independently associated with an increasing number of subclinical cardiovascular injury markers in adolescents.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"992-1001"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515380","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":"Hypertension Management Dynamics in Pediatric CKD: Insights From the 4C Study.","authors":"Anke Doyon, Aysun Karabay Bayazit, Ali Duzova, Daniela Thurn, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Lukasz Obrycki, Bruno Ranchin, Rukshana Shroff, Cengiz Candan, Hakan Erdogan, Dusan Paripovic, Osman Donmez, Francesca Lugani, Klaus Arbeiter, Ebru Yilmaz, Ariane Zaloszyc, Elke Wühl, Anette Melk, Uwe Querfeld, Franz Schaefer","doi":"10.1161/HYPERTENSIONAHA.124.24330","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24330","url":null,"abstract":"<p><strong>Background: </strong>Office blood pressure (BP) trajectories may help assess hypertension progression and the effects of antihypertensive treatment in children with chronic kidney disease.</p><p><strong>Methods: </strong>Analysis of antihypertensive treatment and BP slopes in 320 patients from the 4C study (Cardiovascular Comorbidity in Children with Chronic Kidney Disease) cohort with chronic kidney disease before renal replacement therapy, based on a minimum of 3 individual observations and 2 years of follow-up.</p><p><strong>Results: </strong>At enrollment, 70 (22%) patients had uncontrolled or untreated hypertension, 130 (41%) patients had controlled hypertension, and 120 (37%) patients had normotension without antihypertensive treatment. Antihypertensive treatment medication was prescribed for 53% of patients at baseline and initiated or added for 91 patients (AHT-I [group with intensification of antihypertensive treatment] group, 28%) during follow-up. Overall BP SD score remained stable over time in the cohort (β=-0.037±0.034, <i>P</i>=0.34 and -0.029±0.348, <i>P</i>=0.093 per year for systolic and diastolic BP SD score). In the AHT-I group, systolic and diastolic BP SD scores were higher at baseline and decreased significantly during follow-up (-0.22±0.07, <i>P</i><0.003 and -0.12±0.05 SD score per year, <i>P</i>=0.01). Only 8 of 70 (11%) patients from the previously untreated/uncontrolled group remained untreated at the last observation, while 31 (44%) were controlled during follow-up. Of the 120 normotensive patients at baseline, 60% remained normotensive while 40% progressed to uncontrolled/untreated (n=23, 19%) or controlled (n=24, 20%) hypertension.</p><p><strong>Conclusions: </strong>Although the overall BP of the population remained stable over time, individual patterns of BP management showed considerable variability. BP control improved significantly with intensified antihypertensive therapy; however, a significant number of previously normotensive individuals developed new-onset hypertension during the observation period.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1035-1045"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803271","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":"Nationwide, Pragmatic, Direct-to-Patient Primary Aldosteronism Testing Program.","authors":"Jenifer M Brown, Laura C Tsai, Eva E Abel, Arnaldo Ferrebus, Anna E Moore, Yvonne M Niebuhr, Bassil Bacare, Brooke Honzel, Julia Milks, Kristen Foote, Andrew J Newman, Wasita W Parksook, Anand Vaidya","doi":"10.1161/HYPERTENSIONAHA.125.24648","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24648","url":null,"abstract":"<p><strong>Background: </strong>Primary aldosteronism, an endocrinopathy present in ≥10% to 25% of patients with hypertension, confers excess cardiovascular risk that can be mitigated with aldosterone-directed therapy. However, only 2% of eligible patients undergo guideline-recommended screening. This study aimed to bypass clinical inertia and identify people with primary aldosteronism using pragmatic, direct-to-patient testing.</p><p><strong>Methods: </strong>Hypertensive adults were recruited via online platforms and underwent virtual consent and local phlebotomy. Using a standardized diagnostic algorithm, laboratory results with interpretations were communicated to patients and primary care providers. Follow-up was ascertained at 6 to 12 months. The primary outcome was the frequency of a positive test for primary aldosteronism. Secondary outcomes included follow-up primary aldosteronism testing and implementation of aldosterone-targeted therapies.</p><p><strong>Results: </strong>The study population (N=694) had a mean age of 63.3±11.3 years, was 52.2% female, and hailed from 41 US states. Overall, 25.4% had a positive test for primary aldosteronism. Sleep apnea, resistant hypertension, and hypokalemia were the most common testing indications, with 55.2% of participants having ≥2 indications. Over half of participants (57%) were already under endocrinology, cardiology, or nephrology care, yet had not been tested. In longitudinal follow-up of participants with a positive result, 25.5% had additional testing, 13.7% were started on aldosterone-targeted therapy (mineralocorticoid receptor antagonist or adrenalectomy), and 24.5% reported improved blood pressure control.</p><p><strong>Conclusions: </strong>Pragmatic, direct-to-patient testing, and simplified results interpretation is a feasible, scalable method to increase primary aldosteronism diagnoses and implementation of aldosterone-targeted therapies. Given that new hypertension guidelines recommend primary aldosteronism screening in all hypertensive people, practical approaches to test, interpret, and implement results will be essential.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"977-988"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467878","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":"ACLY Promotes Cardiac Fibrosis via the Regulation of DNL and Histone Acetylation.","authors":"Naoya Kuwahara, Manabu Nagao, Masakazu Shinohara, Kenta Kaneshiro, Takuo Emoto, Takeshi Yoshida, Terunobu Fukuda, Makoto Nishimori, Seimi Satomi-Kobayashi, Hiromasa Otake, Ken-Ichi Hirata, Tatsuro Ishida, Ryuji Toh","doi":"10.1161/HYPERTENSIONAHA.124.24088","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24088","url":null,"abstract":"<p><strong>Background: </strong>ATP citrate lyase (ACLY) is a key enzyme in de novo lipogenesis that generates acetyl-CoA from citrate. Although fatty acids are required for energy production and biomass synthesis in the heart, the regulatory mechanisms of ACLY-mediated de novo lipogenesis in pathological cardiac fibroblasts remain unknown. The aim of this study was to investigate the biological role of ACLY in cardiac remodeling.</p><p><strong>Methods: </strong>Adeno-associated virus serotype 9-mediated shRNA targeting <i>Acly</i> was intravenously injected into C57BL/6J male mice. The mice were subsequently continuously infused with a mixture of angiotensin II and phenylephrine. Cardiac phenotypes were evaluated via histological staining. Cell proliferation assays, stable isotope tracing with 13C-labeled glucose, and chromatin immunoprecipitation assays were performed using human cardiac fibroblasts.</p><p><strong>Results: </strong>ACLY expression was upregulated in the heart sections of mice treated with angiotensin II/phenylephrine, in particular in fibrotic areas. Masson trichrome staining revealed that <i>Acly</i> gene silencing significantly reduced cardiac fibrosis in these mice. Both siRNA-mediated <i>ACLY</i> knockdown and pharmacological ACLY inhibition suppressed the proliferation and expression of fibrous proteins in cultured human cardiac fibroblasts stimulated with transforming growth factor-β. Mechanistically, ACLY inhibition reduced de novo lipogenesis, limiting the fatty acid supply essential for cellular growth and proliferation. It also decreased H3K9 and H3K27 acetylation, in addition to the presence of acetylated H3K9 and H3K27 at the promoter regions of fibrotic genes.</p><p><strong>Conclusions: </strong>Our findings demonstrate that ACLY plays an important role in maladaptive cardiac fibrosis. ACLY could be a novel therapeutic target to prevent the development of heart failure.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1116-1128"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566883","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":"Identification of Novel Therapeutic Targets for Hypertension.","authors":"Zhiwei Zheng, Rumeng Chen, Menghua Liu, Yining Ding, Shuling Xu, Chunyan Hou, Sen Li","doi":"10.1161/HYPERTENSIONAHA.124.24277","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24277","url":null,"abstract":"<p><strong>Background: </strong>Persistently high blood pressure remains the leading risk factor for mortality worldwide. This study aims to identify potential drug targets for hypertension.</p><p><strong>Methods: </strong>Mendelian randomization was used to identify therapeutic targets for hypertension. Genome-wide association study summary statistics were obtained from the UK Biobank and FinnGen study. Cis-expression quantitative trait loci from the eQTLGen Consortium served as genetic instruments. Colocalization analysis evaluated the likelihood of shared causal variants between single-nucleotide polymorphisms influencing hypertension and gene expression. Survival analysis of UK Biobank data assessed hypertension and mortality risks across participants with different gene alleles.</p><p><strong>Results: </strong>Mendelian randomization analysis identified 190 drug targets in the discovery cohort and 65 in the replication cohort after multiple testing correction. Colocalization analysis identified 14 hypertension-related drug targets, including ACE, AIMP1, CDC25A, EHMT2, FES, GPX1, GRK4, HSD3B7, NEK4, PTPN12, SIK2, SLC22A4, SLC2A4, and TNFSF12. Survival analysis revealed individuals with the A allele at rs4308 in the <i>ACE</i> gene had a higher incidence of hypertension, while those with the T allele at rs11242109 in the <i>SLC22A4</i> gene showed a lower hypertension-specific mortality rate.</p><p><strong>Conclusions: </strong>Drug target Mendelian randomization studies offer new directions for hypertension treatment, providing insights into its mechanisms and robust targets for developing antihypertensive drugs.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1056-1070"},"PeriodicalIF":6.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663561","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}