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Mechanisms of Elevated Cutaneous Vascular Tone in College-Aged Black Individuals. 大学年龄黑人皮肤血管张力升高的机制。
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1161/HYPERTENSIONAHA.125.24701
John D Akins, Rauchelle E Richey, Zachary T Martin, Paul J Fadel, R Matthew Brothers
{"title":"Mechanisms of Elevated Cutaneous Vascular Tone in College-Aged Black Individuals.","authors":"John D Akins, Rauchelle E Richey, Zachary T Martin, Paul J Fadel, R Matthew Brothers","doi":"10.1161/HYPERTENSIONAHA.125.24701","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24701","url":null,"abstract":"<p><strong>Background: </strong>Hypertension prevalence is greatest in the US non-Hispanic Black population, possibly through reduced vascular function. Although heightened cutaneous vascular tone and vasoconstrictor responsiveness have been reported in Black individuals, the underlying physiological mechanisms remain unknown.</p><p><strong>Methods: </strong>Thirteen Black (6 women, 22±2 years) and 10 non-Hispanic White (4 women, 25±4 years) participants underwent intradermal perfusion of norepinephrine alone (10<sup>-</sup><sup>8</sup> to 10<sup>-</sup><sup>2</sup> M; control) or coinfused with ascorbic acid (general antioxidant), L-NAME (<i>N</i><sup>ω</sup>-nitro- L-arginine methyl ester; a nitric oxide synthase inhibitor), or combined ascorbic acid and l-NAME. Cutaneous vascular conductance was used to estimate vascular tone.</p><p><strong>Results: </strong>Non-Hispanic Black participants had lower absolute conductance at the control (<i>P</i>=0.012), but not ascorbic acid or l-NAME sites (both <i>P</i>>0.123). Black participants also had lower absolute baseline conductance at all sites (0.26±0.13 versus 0.37±0.14 flux/mm Hg) and across the norepinephrine perfusions (≈51% lower; both <i>P</i><0.05). At baseline and across norepinephrine perfusions, ascorbic acid increased absolute conductance compared with control in both groups (Black: +94%; White: +39%), while l-NAME reduced absolute conductance in the White participants only (-43%; all <i>P</i><0.05). Across all doses, control relative conductance was not different between the groups (<i>P</i>>0.05), though the ascorbic acid and combined sites in the Black participants and all sites in the White participants produced greater relative conductance than control (all <i>P</i><0.05).</p><p><strong>Conclusions: </strong>These data suggest greater tonic, but not norepinephrine-induced, cutaneous vasoconstriction in Black individuals, which appears to be mediated by greater oxidative stress contributing to reduced nitric oxide bioavailability.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1675-1686"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882803","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}
引用次数: 0
Debate on the 2025 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: New Blood Pressure Targets, Lower Is Better-And Possible. 关于2025年成人高血压预防、检测、评估和管理指南的讨论:新的血压目标,越低越好-而且是可能的。
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-28 DOI: 10.1161/HYPERTENSIONAHA.125.25466
Lucas Lauder, Kazem Rahimi, Michael Böhm, Felix Mahfoud
{"title":"Debate on the 2025 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: New Blood Pressure Targets, Lower Is Better-And Possible.","authors":"Lucas Lauder, Kazem Rahimi, Michael Böhm, Felix Mahfoud","doi":"10.1161/HYPERTENSIONAHA.125.25466","DOIUrl":"10.1161/HYPERTENSIONAHA.125.25466","url":null,"abstract":"<p><p>The American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guideline has now released the long-awaited 2025 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Since the previous version, which had been in place for 8 years, meta-analyses and several treat-to-target trials investigating lower versus standard blood pressure targets have been published. Based on these, the 2025 American College of Cardiology/American Heart Association guideline recommends in adults with confirmed hypertension, an office blood pressure goal of <130/80 mm Hg, with encouragement to further reduce systolic blood pressure to <120 mm Hg. Here, we set out why we support these lower blood pressure targets and outline strategies to achieve them.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1551-1558"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952114","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}
引用次数: 0
Cellular Senescence Mediates Doxorubicin Chemotherapy-Induced Aortic Stiffening: Role of Glycation Stress. 细胞衰老介导阿霉素化疗诱导的主动脉硬化:糖基化应激的作用。
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI: 10.1161/HYPERTENSIONAHA.125.25408
Ravinandan Venkatasubramanian, Mary A Darrah, Sophia A Mahoney, David A Hutton, Grace S Maurer, Katelyn R Ludwig, Nicholas S Van Dongen, Nathan T Greenberg, Abigail G Longtine, Vienna E Brunt, Parminder Singh, James J Galligan, Marissa N Trujillo, Pankaj Kapahi, Simon Melov, Matthew J Rossman, Douglas R Seals, Zachary S Clayton
{"title":"Cellular Senescence Mediates Doxorubicin Chemotherapy-Induced Aortic Stiffening: Role of Glycation Stress.","authors":"Ravinandan Venkatasubramanian, Mary A Darrah, Sophia A Mahoney, David A Hutton, Grace S Maurer, Katelyn R Ludwig, Nicholas S Van Dongen, Nathan T Greenberg, Abigail G Longtine, Vienna E Brunt, Parminder Singh, James J Galligan, Marissa N Trujillo, Pankaj Kapahi, Simon Melov, Matthew J Rossman, Douglas R Seals, Zachary S Clayton","doi":"10.1161/HYPERTENSIONAHA.125.25408","DOIUrl":"10.1161/HYPERTENSIONAHA.125.25408","url":null,"abstract":"<p><strong>Background: </strong>Mechanisms underlying doxorubicin chemotherapy-induced aortic stiffening are incompletely understood. To determine the role of cellular senescence and the senescence-associated secretory phenotype (SASP) in mediating doxorubicin-induced aortic stiffening and the influence of senolytic therapy.</p><p><strong>Methods: </strong>Aortic stiffness (aortic pulse wave velocity) and associated mechanisms were assessed in young adult p16-3MR mice, a model that allows for genetic-based clearance of senescent cells with ganciclovir. Young (4-6 months) mice were injected with doxorubicin and subsequently treated with ganciclovir or the senolytic ABT263. We evaluated the influence of SASP-associated circulating factors in plasma (the circulating SASP milieu) in mediating aortic stiffening ex vivo (aortic elastic modulus) and examined the contribution of glycation stress.</p><p><strong>Results: </strong>Doxorubicin increased aortic pulse wave velocity (425±6 versus control, 353±5 cm/s; <i>P</i><0.0001), an effect prevented by both ganciclovir (348±4 cm/s) and ABT263 (342±7 cm/s; <i>P</i><0.0001 for both versus doxorubicin). Plasma from doxorubicin-treated mice induced aortic stiffening ex vivo (<i>P</i>=0.02 versus plasma from control mice), whereas plasma from doxorubicin-ganciclovir and doxorubicin-ABT263 groups did not. Glycation stress was implicated in SASP-mediated aortic stiffening with doxorubicin, as inhibition of receptor-mediated glycation stress signaling attenuated plasma-induced aortic stiffening.</p><p><strong>Conclusions: </strong>Cellular senescence and the circulating SASP milieu contribute to doxorubicin-induced aortic stiffening. Senolytics hold promise for preserving aortic stiffening following doxorubicin exposure.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1767-1777"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12327803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759895","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}
引用次数: 0
Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia. 大规模蛋白质组学揭示了迟发性子痫前期新的候选生物标志物。
IF 8.3 1区 医学
Hypertension Pub Date : 2025-10-01 DOI: 10.1161/hypertensionaha.125.25189
Ina J Andresen,Roberto Romero,Ane C Westerberg,Nándor Gábor Than,Nardhy Gomez-Lopez,Gaurav Bhatti,Oladejo Ahmodu,Dereje W Gudicha,Arun Meyyazhagan,Awoniyi Awonuga,Tinnakorn Chaiworapongsa,David R Bryant,Trond M Michelsen,Adi L Tarca
{"title":"Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia.","authors":"Ina J Andresen,Roberto Romero,Ane C Westerberg,Nándor Gábor Than,Nardhy Gomez-Lopez,Gaurav Bhatti,Oladejo Ahmodu,Dereje W Gudicha,Arun Meyyazhagan,Awoniyi Awonuga,Tinnakorn Chaiworapongsa,David R Bryant,Trond M Michelsen,Adi L Tarca","doi":"10.1161/hypertensionaha.125.25189","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25189","url":null,"abstract":"BACKGROUNDPreeclampsia is classified as either a more severe early onset or a more prevalent late-onset form. Lower PlGF (placental growth factor) and increased sFlt-1 (fms-like tyrosine kinase-1) in maternal circulation are promising biomarkers, yet they lack specificity for preeclampsia.METHODSWe quantified ≈7000 proteins in 673 samples collected from 89 patients with late-onset preeclampsia and 91 controls at T1 (15-22), T2 (22-30), and T3 (30-42) weeks. Elastic net and random forest models were fitted and evaluated by cross-validation. Differential abundance analysis followed by functional profiling, was used to identify and interpret protein changes.RESULTSAn increase in protein differential abundance in late-onset preeclampsia was observed with advancing gestation, reaching 806 proteins at T3 related to angiogenesis, cell adhesion, and extracellular matrix remodeling. FAAH2 (fatty acid amide hydrolase 2), SIGLEC6 (sialic acid-binding Ig-like lectin-6), IL17RC (interleukin-17 receptor C), HTRA1 (serine protease), sFlt-1, and 47 other proteins dysregulated at T3 were validated in a reanalysis of a ≈5000 protein Norwegian data set. Random forest models with 20 proteins showed high accuracy at T3 (area under the curve [AUC], 0.83 [0.77-0.89], sensitivity 59%) even in cases not yet diagnosed at sampling (n=31, AUC, 0.80 [0.71-0.90], sensitivity 58%), outperforming sFlt-1 and PlGF. Moderate accuracy was obtained at T1 (AUC, 0.63 [0.54-0.72], sensitivity 33%) and T2 (AUC, 0.59 [0.50-0.68], sensitivity 17%). Combining maternal characteristics and obstetric history with proteomics data increased accuracy at T1 (AUC, 0.68 [0.59-0.77], sensitivity 28%), T2 (AUC, 0.68 [0.60-0.77], sensitivity 31%), and T3 (AUC, 0.87 [0.81-0.92], sensitivity 69%).CONCLUSIONSThe findings confirm the involvement of abnormal trophoblast invasion, angiogenesis, and extracellular matrix remodeling in late-onset preeclampsia, while highlighting new protein alterations consistent across diverse cohorts.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"1 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194448","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}
引用次数: 0
Inducible Endothelial Gch1 Deletion Reveals Rapid, Sex-Specific Effects on Blood Pressure and Pregnancy Outcomes. 诱导内皮细胞Gch1缺失对血压和妊娠结局的快速、性别特异性影响
IF 8.3 1区 医学
Hypertension Pub Date : 2025-10-01 DOI: 10.1161/hypertensionaha.125.25058
Surawee Chuaiphichai,Desson Au-Yeung,Christopher A R Whiteman,Sarah L Cook,Eileen McNeill,Gillian Douglas,Keith M Channon
{"title":"Inducible Endothelial Gch1 Deletion Reveals Rapid, Sex-Specific Effects on Blood Pressure and Pregnancy Outcomes.","authors":"Surawee Chuaiphichai,Desson Au-Yeung,Christopher A R Whiteman,Sarah L Cook,Eileen McNeill,Gillian Douglas,Keith M Channon","doi":"10.1161/hypertensionaha.125.25058","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25058","url":null,"abstract":"BACKGROUNDTetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide synthase. Constitutive endothelial BH4 deficiency leads to mild hypertension and vascular dysfunction that are partly compensated by alternative endothelium-derived vasodilators. Accordingly, we generated a novel VE-Cadherin-CreERT2 (VE-Cad-Cre) mouse to evaluate the impact of inducing endothelial-specific BH4 deficiency in adult animals, without the potential mitigating effects of developmental or other adaptive mechanisms.METHODSEndothelial Gch1 deletion and BH4 deficiency were induced by tamoxifen administration to Gch1fl/flVE-Cad-Cre male and female adult mice. In female mice, endothelial BH4 deficiency was also induced immediately before pregnancy. The effects of inducible Gch1 deletion were determined on BH4 levels, vascular function, blood pressure, and fetal development during pregnancy.RESULTSMale and female Gch1fl/flVE-Cad-Cre mice had normal blood pressure. However, tamoxifen treatment of male Gch1fl/flVE-Cad-Cre mice caused progressive hypertension with impaired nitric oxide synthase-mediated vasodilation. Tamoxifen treatment of female Gch1fl/flVE-Cad-Cre mice led to nonprogressive hypertension that was exacerbated by pregnancy, leading to impaired uteroplacental vascular function and fetal growth restriction.CONCLUSIONSInduction of endothelial cell BH4 deficiency reveals rapid, sex-specific requirements for endothelial cell BH4 in vascular function and blood pressure, and the cardiovascular response to pregnancy. These changes are more striking than those reported for constitutive endothelial cell BH4 deficiency, suggesting a role for developmental or other adaptive effects that fail to mitigate the effects of inducible endothelial cell BH4 deficiency. Targeting endothelial BH4 bioavailability may offer therapeutic strategies for acquired hypertensive disorders and fetal growth restriction.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"11 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194885","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}
引用次数: 0
Use of Risk Assessment to Guide Decision-Making for Blood Pressure Management in the Primary Prevention of Cardiovascular Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. 在心血管疾病一级预防中使用风险评估来指导血压管理决策:美国心脏协会和美国心脏病学会的科学声明
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-28 DOI: 10.1161/HYP.0000000000000248
Sadiya S Khan, Marwah Abdalla, Natalie A Bello, Ciantel A Blyler, Jocelyn Carter, Yvonne Commodore-Mensah, Keith C Ferdinand, Heather M Johnson, Daniel Jones, Amit Khera, Paul Muntner, Stacey Schott, Daichi Shimbo, Sidney C Smith, Sandra J Taler, Eugene Yang, Donald M Lloyd-Jones
{"title":"Use of Risk Assessment to Guide Decision-Making for Blood Pressure Management in the Primary Prevention of Cardiovascular Disease: A Scientific Statement From the American Heart Association and American College of Cardiology.","authors":"Sadiya S Khan, Marwah Abdalla, Natalie A Bello, Ciantel A Blyler, Jocelyn Carter, Yvonne Commodore-Mensah, Keith C Ferdinand, Heather M Johnson, Daniel Jones, Amit Khera, Paul Muntner, Stacey Schott, Daichi Shimbo, Sidney C Smith, Sandra J Taler, Eugene Yang, Donald M Lloyd-Jones","doi":"10.1161/HYP.0000000000000248","DOIUrl":"10.1161/HYP.0000000000000248","url":null,"abstract":"<p><p>Risk assessment plays a central role in the primary prevention of cardiovascular disease. The 2017 High Blood Pressure Clinical Practice Guideline incorporated quantitative risk assessment for the first time to guide the initiation of antihypertensive drug therapy and recommended calculation of 10-year risk of atherosclerotic cardiovascular disease with the Pooled Cohort Equations. Although the 2025 High Blood Pressure Guideline reaffirmed this overarching paradigm for risk-based initiation of antihypertensive drug therapy, it updated the recommended risk model to the Predicting Risk of Cardiovascular Disease Events equations, which estimate 10-year risk of total cardiovascular disease (including atherosclerotic cardiovascular disease and heart failure), and defined a new risk threshold for initiation of antihypertensive therapy in patients with stage 1 hypertension. This American Heart Association/American College of Cardiology scientific statement summarizes the rationale to recommend the use of the Predicting Risk of Cardiovascular Disease Events equations, the evidence base for the new threshold of 10-year risk of cardiovascular disease of ≥7.5%, and the population-level implications of these revised recommendations. This scientific statement also offers practical advice for implementing risk assessment as the first step in the comprehensive approach to hypertension management with shared decision-making between patients and clinicians. Remaining gaps in awareness and treatment of hypertension underscore the need for innovative strategies to improve implementation of and adherence to risk-based guideline recommendations, including automation of risk assessment in electronic health records, decision-support aids, and refinement of risk assessment, to equitably improve the initiation of antihypertensive drug therapy, blood pressure control, and outcomes.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e317-e336"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952150","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}
引用次数: 0
Implementing the 2025 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: How to Translate Team-Based Care of Hypertension to the Real World. 实施2025年成人高血压预防、检测、评估和管理指南:如何将高血压团队护理转化为现实世界。
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI: 10.1161/HYPERTENSIONAHA.125.25464
Gregory L Hundemer, Rémi Goupil
{"title":"Implementing the 2025 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: How to Translate Team-Based Care of Hypertension to the Real World.","authors":"Gregory L Hundemer, Rémi Goupil","doi":"10.1161/HYPERTENSIONAHA.125.25464","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.25464","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"82 10","pages":"1535-1537"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080412","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}
引用次数: 0
Antiferroptotic Drugs Reduce sFlt-1 Release and Placenta Damage in Preeclampsia. 抗降铁药物减少子痫前期sFlt-1释放和胎盘损伤。
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-19 DOI: 10.1161/HYPERTENSIONAHA.125.25003
Sapir Lianski, Tehila Mizrachi, Oren Barak, Lilah Tsaitlin-Mor, Shirin Elhaik-Goldman, Simcha Yagel, Debra Goldman-Wohl, Sarah M Cohen, Ruth Hefetz Medina, Jacob Rachmilewitz, Haim Michael Barr, Alexander Plotnikov, Yulia Y Tyurina, Vladimir A Tyurin, Svetlana N Samovich, Alexander A Kapralov, S Ananth Karumanchi, Valerian E Kagan, Hülya Bayir, Yoel Sadovsky, Ofer Beharier
{"title":"Antiferroptotic Drugs Reduce sFlt-1 Release and Placenta Damage in Preeclampsia.","authors":"Sapir Lianski, Tehila Mizrachi, Oren Barak, Lilah Tsaitlin-Mor, Shirin Elhaik-Goldman, Simcha Yagel, Debra Goldman-Wohl, Sarah M Cohen, Ruth Hefetz Medina, Jacob Rachmilewitz, Haim Michael Barr, Alexander Plotnikov, Yulia Y Tyurina, Vladimir A Tyurin, Svetlana N Samovich, Alexander A Kapralov, S Ananth Karumanchi, Valerian E Kagan, Hülya Bayir, Yoel Sadovsky, Ofer Beharier","doi":"10.1161/HYPERTENSIONAHA.125.25003","DOIUrl":"10.1161/HYPERTENSIONAHA.125.25003","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is characterized by hypertension, proteinuria, and elevated antiangiogenic sFlt-1 (soluble fms-like tyrosine kinase-1) levels. Despite extensive research, mechanisms underlying sFlt-1 dysregulation remain unclear. This hypothesis-testing study investigated whether ferroptosis, a lipid peroxidation-driven cell death mechanism, contributes to preeclamptic placental pathogenesis and sFlt-1 release, and whether drug repurposing could identify novel therapeutic options.</p><p><strong>Methods: </strong>We analyzed oxidized phosphatidylethanolamines in human preeclamptic and healthy placental tissues using redox phospholipidomics. In placental explants, we evaluated ferroptosis effects on sFlt-1 release using Ferrostatin-1 and deferoxamine as inhibitors. We screened 6520 drugs and compounds to identify effective ferroptosis inhibitors in primary trophoblasts. Statistical analyses used Student <i>t</i> test and 1-way ANOVA with multiple comparison corrections.</p><p><strong>Results: </strong>Preeclamptic placentas showed significant accumulation of oxidized phosphatidylethanolamines compared with controls. Inducing ferroptosis in placental explants increased sFlt-1 release, while inhibition using Ferrostatin-1 and deferoxamine reduced sFlt-1 levels (<i>P</i><0.01). Our screen identified dipyridamole and promethazine as potent ferroptosis inhibitors, reducing lipid peroxidation, preserving glutathione levels, and decreasing sFlt-1 release in preeclamptic explants.</p><p><strong>Conclusions: </strong>This study establishes placental ferroptosis as a key mechanism in early preeclampsia and demonstrates its direct link to sFlt-1 dysregulation. Our systematic drug screening approach identified approved drugs with antiferroptotic activity, suggesting a novel therapeutic strategy for preeclampsia management through drug repurposing. Further research is needed to establish optimal dosing and confirm efficacy in vivo.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1705-1718"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872995","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}
引用次数: 0
Debate on the 2025 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Emphasis on Defense Against the BP Threshold and Why We May Not Get There Easily. 关于2025年成人高血压预防、检测、评估和管理指南的辩论:强调防御血压阈值以及为什么我们可能不容易达到这个阈值
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-28 DOI: 10.1161/HYPERTENSIONAHA.125.25468
Raymond R Townsend
{"title":"Debate on the 2025 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Emphasis on Defense Against the BP Threshold and Why We May Not Get There Easily.","authors":"Raymond R Townsend","doi":"10.1161/HYPERTENSIONAHA.125.25468","DOIUrl":"10.1161/HYPERTENSIONAHA.125.25468","url":null,"abstract":"<p><p>Elevated blood pressure (BP) is the most important noncommunicable disorder worldwide. Finding and effectively managing elevated BP is the single greatest public health benefit we can accomplish, as it will reduce premature death and enable patients to live longer free of the disabilities that target organ damage inflicts on the brain, heart, kidneys, and legs. Hypertension guidelines are an invaluable source of information on how to detect elevated BP, how to evaluate people for situations where hypertension is a symptom of other disorders, and how to apply the various treatments that lower BP effectively in patients. Determining the point at which treating high BP is more likely to result in benefit than harm is a marriage of science and art. There is no right answer to what clearly constitutes hypertension when using a systolic or diastolic BP to define it. The science shows the mathematics behind the reduction of BP and the number of lives saved and target organs preserved. The art comes into play when a decision is made that, when a systolic or diastolic BP exceeds a certain level, it becomes reasonable to intervene at that point with treatment. Caregivers play an important role in monitoring and educating patients with hypertension-especially in the detection of unintended effects of treatment, such as excessive BP lowering, symptomatic hypotension, and impacts on laboratory tests and well-being. Nonadherence to prescribed therapies is a barrier to effectively managing chronic disorders like hypertension. Having a solid foundation in the science behind the guidelines and recognizing that the application of guidelines requires some clinical judgment gleaned from balancing the risks and benefits of treatment in each individual patient, is the basis for healthy exchanges of ideas, like this pro and con series which discusses the science and furthers the art. This review has taken the con side of several issues in the latest American College of Cardiology/American Heart Association 2025 Hypertension Guideline.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1559-1568"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952102","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}
引用次数: 0
Food as Medicine for Hypertension: Microbiota as Mediators. 食物作为高血压的药物:微生物群作为介质。
IF 8.2 1区 医学
Hypertension Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1161/HYPERTENSIONAHA.125.17950
Zaina Kret, Oluwatosin Mautin Akinola, Wisdom Ahlidja, Bina Joe
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