Hypertension最新文献

{"title":"NICD4/USP8-Positive Feedback Loop Contributes to the Development of Hypoxic Pulmonary Hypertension.","authors":"Mingzhou Guo, Ke Li, Yuchen Huang, Xuezhao Wang, Yuanzhou He, Congyi Wang, Jianping Zhao, Xiansheng Liu, Xiaochen Li","doi":"10.1161/HYPERTENSIONAHA.125.25501","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.25501","url":null,"abstract":"<p><strong>Background: </strong>Hypoxic pulmonary hypertension (HPH) is a representative vascular remodeling disease with a poor prognosis. Previous findings from our study have implicated the NICD4 (NOTCH4 intracellular domain) in pulmonary artery smooth muscle cells (PASMCs) in the pathogenesis of HPH. However, the underlying regulatory mechanisms remain unclear. In this study, we aimed to elucidate the potential regulatory mechanism of NICD4 in HPH.</p><p><strong>Methods: </strong>Using coimmunoprecipitation combined with mass spectrometry, we identified USP8 (ubiquitin-specific peptidase 8) as a novel binding protein of NICD4 in PASMCs. The functional role of USP8 was investigated in vivo using smooth muscle cell-specific <i>Usp8</i> knockout (Usp8^<i>Acta</i>2^<i>-/-</i>) mice and in vitro using primarily cultured PASMCs, alongside pharmacological inhibition with DUB-IN-2.</p><p><strong>Results: </strong>USP8 was significantly upregulated in lung tissues from patients with HPH due to interstitial lung disease or chronic obstructive pulmonary disease, HPH rodent models, as well as in hypoxic PASMCs. <i>Usp8</i> deficiency in Acta2-positive mice (Usp8^{<i>Acta</i>2<i>-</i>}^<i>/-</i>) or pharmacological inhibition of USP8 by DUB-IN-2 markedly attenuated HPH development. In vitro, USP8 knockdown suppressed hypoxia-induced PASMC proliferation, migration, and apoptosis resistance by modulating the NICD4-MAPK pathway. Mechanistically, USP8 was bound directly to NICD4 to maintain its stability by removing the K48-linked ubiquitin chain on NICD4 at lysine 1760, thus preventing proteasomal degradation. Furthermore, <i>USP8</i> can be transcriptionally upregulated by CSL/NICD4 under hypoxia, forming a NICD4/USP8-positive feedback loop.</p><p><strong>Conclusions: </strong>Our study unveils a critical NICD4/USP8-positive feedback loop that drives HPH pathogenesis, highlighting the importance of ubiquitination in pulmonary vascular remodeling. Targeted disruption of this loop represents a promising therapeutic strategy for HPH.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837151","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":"Real-Time Evaluation of Gastrointestinal pH and Transit Time in Patients With Essential Hypertension.","authors":"Evany Dinakis, Liang Xie, Dakota Rhys-Jones, Dovile Anderson, C K Yao, Daniel So, Darren J Creek, Peter R Gibson, Jane Muir, Francine Z Marques","doi":"10.1161/HYPERTENSIONAHA.126.26670","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.126.26670","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837242","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":"Impaired Midkine/Treg Signaling Contributes to Pathogenesis of Preeclampsia.","authors":"Liqun Lou, Ye Chen, Shengyi Gu, Jingrong Chen, Yang Lu, Junlong Dang, Shi Qin, Sheng Wan, Chenchen Zhou, Weijia Luo, Wenxi He, Song Guo Zheng, Xiaolin Hua","doi":"10.1161/HYPERTENSIONAHA.125.25910","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.25910","url":null,"abstract":"<p><strong>Background: </strong>Early-onset preeclampsia is characterized by maternal-fetal immune dysregulation and trophoblast dysfunction, commonly presenting with a reduction in regulatory T cells (Tregs) and impaired trophoblast invasion. However, the precise role of aberrant Treg-trophoblast communication in early-onset preeclampsia progression remains unclear.</p><p><strong>Methods: </strong>A preeclampsia-like syndrome mouse model was established by administration of the nitric oxide inhibitor, NG-nitroarginine methyl ester hydrochloride. Mouse natural Tregs were adoptively transferred into the NG-nitroarginine methyl ester hydrochloride model via tail vein injection. Confirmatory experiments were conducted using an additional preeclampsia-like syndrome model generated by the administration of iMDK (MDK [midkine] and PI3K/Akt inhibitor). An in vitro coculture model was established using a trophoblast cell line and human Tregs isolated from both umbilical cord/placental blood and maternal peripheral blood.</p><p><strong>Results: </strong>Placentas from patients with early-onset preeclampsia had reduced numbers of Tregs compared with healthy controls. Adoptive Treg transfer activated the TβR1 (transforming growth factor β type I receptor)/Smad3 signaling pathway in trophoblasts, thereby enhancing their invasive and proliferative capacities and ultimately mitigating preeclampsia-like syndrome. Moreover, maternal peripheral blood MDK levels exhibited a significant inverse correlation with disease severity. MDK upregulates LAP (latency-associated peptide) expression on Tregs and acts synergistically with adoptive Treg transfer, resulting in a more pronounced therapeutic effect than Treg transfer alone.</p><p><strong>Conclusions: </strong>This study demonstrates that restoring Tregs ameliorates preeclampsia-like syndrome by enhancing trophoblast function. We further identify MDK as a key mediator enhancing this therapy, which upregulates LAP expression on Tregs and synergistically improves its overall efficacy against early-onset preeclampsia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837095","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":"Nicotine-Mediated Redox and Nitrosative Stress in Cardiorenal Health.","authors":"Marharyta Semenikhina, Adam Jones, Vishwajeeth Pasham, Milos N Budisavljevic, Oleg Palygin, Daria V Ilatovskaya","doi":"10.1161/HYPERTENSIONAHA.126.26095","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.126.26095","url":null,"abstract":"<p><p>Nicotine exposure is increasingly widespread due to the expansion of the use of noncombustible tobacco and nicotine-replacement products; yet nicotine is still being framed as an addictive but relatively benign compound. This review synthesizes clinical and experimental evidence linking nicotine exposure to cardiorenal disease, emphasizing that risks persist after cessation. We discuss here a central novel concept that damage caused by nicotine in tissues is not determined solely by receptor signaling, as nicotine exists in chemical forms capable of strong receptor-independent membrane diffusion. Mechanistically, we highlight convergent pathways of nicotine-induced cellular injury, focusing on redox stress and underscoring major limitations in the field, such as the lack of studies in epithelial cells. We further emphasize the emerging paradigm that links nicotine and NOS biology, in which reduced nitric oxide bioavailability, NOS uncoupling, and peroxynitrite-mediated protein nitration represent underappreciated drivers of persistent cardiorenal injury in response to nicotine. Finally, we outline gaps and research priorities needed to identify therapeutic strategies that specifically mitigate nicotine-driven oxidative and nitrosative injury in vulnerable populations with hypertension, diabetes, and chronic kidney disease.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837222","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":"Pregnancy-Related Complications in Primary Aldosteronism: A European Survey.","authors":"Vittorio Forestiero, Juan Solorzano Roa, Ester Landau, Julien Riancho, Jacopo Burrello, Elisa Sconfienza, Silvia Monticone, Vassilis Tsatsaris, Martin Reincke, Marcus Quinkler, Michel Azizi, Romain Boulestreau, Paolo Mulatero, Laurence Amar","doi":"10.1161/HYPERTENSIONAHA.125.25339","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.25339","url":null,"abstract":"<p><strong>Background: </strong>Hypertensive disorders of pregnancy represent a major cause of maternal and fetal morbidity and mortality. Despite primary aldosteronism (PA) being the most common cause of secondary hypertension, there is limited data on pregnancy complications in patients with PA.</p><p><strong>Methods: </strong>We conducted an international survey across 5 Hypertension Centers in Europe to gather data on maternal and neonatal complications in women diagnosed with PA from 2000 to 2022. We included 102 women aged 18 to 45 years at PA diagnosis who were pregnant either after or <1-year before the diagnosis of PA. The first eligible pregnancy for each patient was included.</p><p><strong>Results: </strong>Overall, 56% of pregnancies were complicated, with the most frequent complications being maternal preeclampsia (36%), preterm birth (30%), low birth weight (30%), and neonatal intensive care admission (22%). Hypokalemia occurred in 31% of pregnancies. Pregnancies occurring before PA diagnosis presented a poorer blood pressure control and were associated with higher rates of overall, maternal, and fetal/neonatal complications compared with pregnancies in patients with an established PA diagnosis. Independent predictors of complications included uncontrolled blood pressure values during pregnancy (odds ratio [OR], 7.05), undiagnosed PA (OR, 4.37), North/Black African ethnicity (OR, 3.69), a higher body mass index (OR, 1.09), and treatment with a higher number of antihypertensive drugs at PA diagnosis (OR, 2.18).</p><p><strong>Conclusions: </strong>PA is associated with a high rate of pregnancy-related complications, predominantly preeclampsia. Undiagnosed PA during gestation significantly increases the risk of adverse outcomes. Early identification and optimized hypertension control in women with PA are critical to improve maternal and fetal outcomes.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837224","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":"Brachial Pulse Pressure and Outcomes: A Report From the WISE Study.","authors":"Juan Vilaro, Eileen M Handberg, George Sopko, Galen Cook-Wiens, Carl J Pepine, C Noel Bairey Merz","doi":"10.1161/HYPERTENSIONAHA.125.26212","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.26212","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837053","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 Trajectories Among Adults Living in Extreme Poverty: A Population-Based Cohort in Port-au-Prince, Haiti.","authors":"Anju Ogyu, Vanessa Rouzier, Rodney Sufra, Reichling St Sauveur, Kelly Celestin, Guyrlaine Forestal, Fabiola Préval, Suzanne Edwidge Marcellin, Sarine Auguste, Myung Hee Lee, Catherine Bennett, Wheytnie Alexandre, Mark D Huffman, Kenneth A Jamerson, Rodolphe Malebranche, Michel Théard, Marie Marcelle Deschamps, Jean William Pape, Lily D Yan, Margaret L McNairy","doi":"10.1161/HYPERTENSIONAHA.125.26295","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.26295","url":null,"abstract":"<p><strong>Background: </strong>Elevated blood pressure (BP) is the leading cause of death globally, with the greatest burden in low-and-middle income countries. Longitudinal BP data are limited in settings of extreme poverty. We identified longitudinal BP trajectories and associated risk factors in urban Haiti.</p><p><strong>Methods: </strong>We analyzed data from 2073 adults (≥18 years) with ≥3 facility-based BP measurements between March 2019 and April 2025 in the population-based Haiti Cardiovascular Disease Cohort. Demographic, behavioral, and clinical data were collected annually. Participants received routine clinical care based on Ministry of Health guidelines. Latent class growth mixture modeling identified systolic BP trajectory groups. Enrollment characteristics associated with BP trajectory group membership were analyzed using multivariable generalized-logit models.</p><p><strong>Results: </strong>At study enrollment, median age was 43 years (interquartile range, 30-56); 60% were female,100% identified as Black Haitian, and 69% lived on <US$1/d. Over 13 446 facility visits (median follow-up, 3.9 years), we identified 4 systolic BP trajectories based on mean enrollment BP: normal, rising (107 mm Hg, 39.2%, mean change +0.7 mm Hg/y), moderate, rising (126 mm Hg, 34.7%, +1.3 mm Hg/y), high, reduction (151 mm Hg, 19.2%, -1.6 mm Hg/y), and very high, rebound (173 mm Hg, 6.9%, -0.8 mm Hg/y). Antihypertensive medication usage and BP control among participants with hypertension increased. Older age, lower education, and obesity were associated with high, reduction, or very high, rebound BP trajectory groups.</p><p><strong>Conclusions: </strong>In this cohort of young, Black adults in Haiti, we identify 4 BP trajectories, describe increases in antihypertensive medication usage and improvement in BP control, demonstrating BP care is feasible in a low-resourced setting.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837089","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":"Angiogenic Imbalance Models of Preeclampsia: From Mechanisms to Clinics.","authors":"Iman Akbarzadeh, Fatemeh Heidari, Serah Nwoke, Chunyan Liu, Tanja Jankovic-Karasoulos, Lana McClements","doi":"10.1161/HYPERTENSIONAHA.125.26316","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.26316","url":null,"abstract":"<p><p>Preeclampsia is a pregnancy-specific hypertensive disorder, clinically defined by new-onset hypertension with proteinuria or other maternal organ dysfunction. It is a leading cause of maternal and perinatal mortality worldwide and remains an incurable condition, with delivery as the only definitive treatment. The disorder originates in placental dysfunction, characterized by inadequate trophoblast invasion and impaired spiral uterine artery remodeling, resulting in syncytiotrophoblast stress and the release of placenta-derived factors. Increased placental secretion of antiangiogenic factors, including soluble fms-like tyrosine kinase-1 and soluble endoglin, promotes angiogenic imbalance and drives widespread maternal endothelial dysfunction. This narrative review synthesizes findings from human studies and experimental research models used to investigate angiogenic dysregulation in preeclampsia, with particular focus on in vitro and in vivo models, and emerging 3-dimensional placental platforms. In vitro models, such as trophoblast organoids, placenta-on-a-chip devices, and 3-dimensional bioprinted constructs, recapitulate key aspects of the placental microenvironment and enable detailed study of aberrant angiogenesis and how to target it, while reducing reliance on limited primary tissue and improving experimental control. Complementing in vitro models, in vivo models are essential for linking placenta-derived angiogenic imbalance to maternal disease phenotypes, therapeutic responses, and fetal outcomes. This review provides a comprehensive assessment of current literature on models that recapitulate angiogenic imbalance in preeclampsia. We emphasize the importance of integrating bioengineering, cell biology, and clinical insights to improve our understanding of preeclampsia pathogenesis and to develop predictive tools and therapeutic strategies to manage angiogenic dysregulation in preeclampsia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837105","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":"High Salt Intake Enhances the REVERSIR-Induced Recovery of Blood Pressure After Angiotensinogen siRNA Treatment.","authors":"Edwyn O Cruz-López, Richard van Veghel, Ingrid M Garrelds, Anne Kasper, Kelly Wassarman, Ho-Chou Tu, Ivan Zlatev, A H Jan Danser","doi":"10.1161/HYPERTENSIONAHA.125.26638","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.125.26638","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837108","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":"Subtyping of Primary Aldosteronism in Partial Adrenal Vein Sampling: The Relative Aldosterone Secretion Index.","authors":"Federico Bernardo Rossi, Teresa Maria Seccia, Giacomo Rossitto, Gian Paolo Rossi","doi":"10.1161/HYPERTENSIONAHA.126.26988","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.126.26988","url":null,"abstract":"<p><p>Expanded screening with the aldosterone-renin ratio has improved detection of primary aldosteronism, the most common surgically curable cause of arterial hypertension. However, identification of surgically curable primary aldosteronism remains constrained by technical limitations of subtyping by adrenal vein sampling (AVS), as bilateral selectivity often fails. Although alternative biomarkers better than cortisol may help reduce this rate, currently, the failure to achieve bilateral selectivity precludes calculation of the lateralization index and, thus, diverts patients toward lifelong medical therapy. Recent advances have established the relative aldosterone secretion index (RASI) as a physiologically grounded strategy to interpret partially successful AVS. By quantifying aldosterone secretion from each adrenal gland relative to peripheral values and incorporating contralateral suppression, RASI-based interpretation can rescue many AVS studies by enabling subtyping under unilateral selectivity with 80% concordance with the lateralization index, when available. Postoperative outcomes following RASI-guided adrenalectomy approximate those achieved after fully selective AVS, with biochemical cure rates of 85% to 90% and blood pressure improvement in 65% to 75%. Studies published over the past 2 to 3 years have clarified factors influencing RASI performance, including cosyntropin stimulation, variations in aldosterone secretion, and the limited utility of cross-sectional imaging alone for subtype classification. Collectively, the available data support the incorporation of RASI into contemporary AVS interpretation algorithms. As primary aldosteronism management enters a postdetection era, subtyping has emerged as the principal bottleneck to definitive cure. RASI provides a pragmatic, evidence-based means to overcome the imperative dependence on bilateral selectivity while preserving diagnostic accuracy, thereby improving access to adrenalectomy and associated cardiovascular benefits.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837215","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}