Hypertension最新文献

{"title":"Identification of Circulating Proteins Associated With Blood Pressure.","authors":"Siqi Xu, Simin Wen, Xizeng Zong, Shifeng Wen, Jianwei Zhu, Weipeng Zheng, Zhiqiang Wang, Peihua Cao, Zhijiang Liang, Changhai Ding, Yan Zhang, Guangfeng Ruan","doi":"10.1161/HYPERTENSIONAHA.124.24151","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24151","url":null,"abstract":"<p><strong>Background: </strong>Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality.</p><p><strong>Methods: </strong>Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure. Colocalization analyses were then used to investigate whether the circulating proteins and blood pressure traits shared causal genetic variants. To further verify the findings, we subsequently performed Steiger filtering analyses, annotation of protein-altering variants, assessment of overlap between protein quantitative trait loci and expression quantitative trait loci, protein-protein interaction and functional enrichment analyses, and drug target evaluation. To provide more potential biomarkers, we further evaluated the epidemiological associations of 2923 circulating proteins with blood pressure and hypertension by cross-sectional and longitudinal analyses using individual data in the UK Biobank.</p><p><strong>Results: </strong>Mendelian randomization and colocalization analyses identified 121 circulating proteins with putative causal effects on at least 1 blood pressure trait. Many of the identified proteins are enriched in the pathways relevant to blood pressure regulation, and a majority of these proteins are either known drug targets or druggable candidates.</p><p><strong>Conclusions: </strong>This study has uncovered numerous circulating proteins potentially causally associated with blood pressure, providing insights into the regulatory mechanisms of blood pressure and potential therapeutic targets to facilitate blood pressure management.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"333-346"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768565","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":"Irisin Improves Preeclampsia by Promoting Embryo Implantation and Vascular Remodeling.","authors":"Dawei Zhu, Jie Huang, Yujie Wu, Lin Fan, Yijun Liu, Qianwen Zhang, Li Li, Jian Han, Xinghui Liu","doi":"10.1161/HYPERTENSIONAHA.123.22353","DOIUrl":"10.1161/HYPERTENSIONAHA.123.22353","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a pregnancy-specific disorder with unclear pathogenesis. Irisin, a recently identified exercise-induced factor, significantly influences lipid metabolism and cardiovascular function. Nonetheless, its role in trophoblast development during human placentation and the related intracellular signaling pathways remain poorly understood.</p><p><strong>Methods: </strong>We assessed peripheral blood irisin expression in early pregnancy among patients with preeclampsia and its correlation with key clinical indicators. In trophoblast cell lines and mice, we used exogenous irisin and viral knockdown to investigate functional changes. Phosphorylation-specific antibody arrays and dual-luciferase reporter assays were used to explore downstream molecular mechanisms, which were subsequently validated in trophoblast cell lines and relevant gene knockout mice.</p><p><strong>Results: </strong>In early pregnancy, patients with preeclampsia exhibit decreased peripheral blood irisin levels, occurring earlier than traditional predictive markers, such as PLGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1). Furthermore, irisin concentration is positively correlated with proteinuria and abnormal blood pressure during pregnancy. Exogenous irisin significantly enhanced trophoblast cell migration, invasion, and proliferation while inhibiting apoptosis. It also increased STAT (signal transducers and activators of transcription) 4 phosphorylation and its binding to the GLUT (glucose transporter)-3 promoter, resulting in elevated GLUT-3 expression and glucose uptake in trophoblast cells. In vivo, increased peripheral irisin promoted embryo implantation, vascular remodeling, and enhanced glucose uptake, whereas reduced irisin resulted in a preeclampsia-like phenotype characterized by elevated blood pressure, proteinuria, renal-placental dysfunction, adipose accumulation, and restricted fetal growth.</p><p><strong>Conclusions: </strong>Peripheral irisin improves preeclampsia by promoting embryo implantation and vascular remodeling through the activation of the STAT4/GLUT-3 pathway. Reduced peripheral irisin may contribute to preeclampsia-like pathologies. This study supports the advocacy for appropriate exercise during early pregnancy and provides new insights for preeclampsia prevention.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"216-231"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619260","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":"Maternal Hypertension Aggravates Vascular Dysfunction After Injury in Male Adult Offspring Through Transgenerational Transmission of N⁶-Methyladenosine.","authors":"Dezhong Zheng, Jiayi Jiang, Anna Shen, Yixiang Zhong, Yi Zhang, Jiancheng Xiu","doi":"10.1161/HYPERTENSIONAHA.124.23373","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23373","url":null,"abstract":"<p><strong>Background: </strong>Whether maternal hypertension contributes to the enhanced susceptibility to vascular remodeling in adult offspring through epigenetic mechanisms remains unclear. We aimed to address this gap in the literature using a transgenerational mouse model.</p><p><strong>Methods: </strong>Gestational hypertension was induced in pregnant mice using chronic angiotensin II infusion. Blood pressure was monitored using the tail-cuff method. Two months post-delivery, an N⁶-methyladenosine epitranscriptomic microarray analysis was performed on the carotid arteries of second-generation mice. A unilateral carotid artery injury model was used to study the postinjury vascular response in vivo. Furthermore, carotid ultrasonography, immunohistochemistry, and molecular biological parameters were assessed in adult offspring.</p><p><strong>Results: </strong>Exposure to maternal hypertension decreased the birth weight of live pups and increased the fetal death rate. Compared with normal offspring, adult offspring with hypertension had wire-induced injury that led to greater vascular remodeling, which was associated with aggravated inflammation imbalance, fibrosis, and oxidative stress. In addition, aberrant N⁶-methyladenosine methylation, increased N⁶-methyladenosine levels, and increased METTL3 (methyltransferase-like 3) expression were detected in the vessels of offspring with hypertension. Maternal METTL3 deficiency increased the birth weight of live pups with hypertension, improved vascular dysfunction, and alleviated vascular inflammation in adult offspring with hypertension after injury.</p><p><strong>Conclusions: </strong>Maternal hypertension can induce transgenerational transmission of enhanced susceptibility to vascular remodeling, and the possible underlying mechanism is associated with altered METTL3-mediated N⁶-methyladenosine methylation. Therefore, this study reveals the role of epigenetic effects across generations and provides new insights into vascular remodeling causes.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"255-266"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835525","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":"Orthostatic and Standing Hypertension and Risk of Cardiovascular Disease.","authors":"Sean W Dooley, Fredrick Larbi Kwapong, Hannah Col, Ruth-Alma N Turkson-Ocran, Long H Ngo, Jennifer L Cluett, Kenneth J Mukamal, Lewis A Lipsitz, Mingyu Zhang, Natalie R Daya, Elizabeth Selvin, Pamela L Lutsey, Josef Coresh, Beverly Gwen Windham, Lynne E Wagenknecht, Stephen P Juraschek","doi":"10.1161/HYPERTENSIONAHA.124.23409","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23409","url":null,"abstract":"<p><strong>Background: </strong>Orthostatic hypertension is an emerging risk factor for adverse events. Recent consensus statements combine an increase in blood pressure upon standing with standing hypertension, but whether these 2 components have similar risk associations with cardiovascular disease (CVD) is unknown.</p><p><strong>Methods: </strong>The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure during visit 1 (1987-1989). We defined systolic orthostatic increase (a rise in systolic blood pressure [SBP] ≥20 mm Hg, standing minus supine blood pressure) and elevated standing SBP (standing SBP ≥140 mm Hg) to examine the new consensus statement definition (rise in SBP ≥20 mm Hg and standing SBP ≥140 mm Hg). We used Cox regression to examine associations with incident coronary heart disease, heart failure, stroke, fatal coronary heart disease, and all-cause mortality.</p><p><strong>Results: </strong>Of 11 369 participants (56% female; 25% Black adults; mean age, 54 years) without CVD at baseline, 1.8% had systolic orthostatic increases, 20.1% had standing SBP ≥140 mm Hg, and 1.3% had systolic orthostatic increases with standing SBP ≥140 mm Hg. During up to 30 years of follow-up, orthostatic increases were not significantly associated with any of the adverse outcomes of interest, while standing SBP ≥140 mm Hg was significantly associated with all end points. In joint models comparing systolic orthostatic increases and standing SBP ≥140 mm Hg, standing SBP ≥140 mm Hg was significantly associated with a higher risk of CVD, and associations differed significantly from systolic orthostatic increases.</p><p><strong>Conclusions: </strong>Unlike systolic orthostatic increases, standing SBP ≥140 mm Hg was strongly associated with CVD outcomes and death. These differences in CVD risk raise important concerns about combining systolic orthostatic increases and standing SBP ≥140 mm Hg in a consensus definition for orthostatic hypertension.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"382-392"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780179","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":"PP2A Attenuates Thoracic Aneurysm and Dissection in Mouse Models of Marfan Syndrome.","authors":"Xianming Zhou,Qian Xu,Xingjian Hu,Philip A Klenotic,Alejandra Valdivia,Bradley G Leshnower,Nianguo Dong,Goutham Narla,Zhiyong Lin","doi":"10.1161/hypertensionaha.124.23494","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.23494","url":null,"abstract":"BACKGROUNDRecent studies show that hyperactivation of mTOR (mammalian target of rapamycin) signaling plays a causal role in the development of thoracic aortic aneurysm and dissection. Modulation of PP2A (protein phosphatase 2A) activity has been shown to be of significant therapeutic value. In light of the effects that PP2A can exert on the mTOR pathway, we hypothesized that PP2A activation by small-molecule activators of PP2A could mitigate AA progression in Marfan syndrome (MFS).METHODSTwo distinct mouse models of MFS underwent daily oral administration of small-molecule activators of the PP2A compound DT-061 to assess its therapeutic potential. Echocardiography was performed to monitor the growth of the aortic root and ascending aorta. Histological evaluation was performed to assess alterations in the vascular wall. RNA-sequencing, Western blot, and immunostaining were performed to decipher the underlying mechanisms by which DT-061 suppresses AA progression.RESULTSPP2A activity decreased, while mTOR activity increased in both human and mouse aortas with MFS. Concordantly, oral administration of DT-061 increased PP2A activation, reducing aortic expansion in Marfan mice. DT-061 treatment also mitigated medial hypertrophy, elastin breakdown, and extracellular matrix deterioration in the ascending aorta, along with decreased metalloproteinase activities. Mechanistic studies suggest that DT-061 suppresses mTOR signaling and smooth muscle cell dedifferentiation, contributing to its effects on thoracic aortic aneurysm and dissection progression.CONCLUSIONSThese studies demonstrate a pathological role of PP2A activity loss in the cause of MFS and implicate that activation of PP2A may serve as a novel therapeutic strategy to limit MFS progression, including aortic aneurysm formation.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"20 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056833","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":"Sphingosine-1-Phosphate, a Marker of Endothelial Injury and Disease Severity in Preeclampsia.","authors":"Camilla Edvinsson, Federica Piani, Frank Matthes, Lotte Vanherle, Lena Erlandsson, Anja Meissner, Stefan Rocco Hansson","doi":"10.1161/HYPERTENSIONAHA.124.24118","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.124.24118","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a hypertensive pregnancy disorder marked by endothelial damage. Healthy endothelium is covered by a protective glycocalyx layer, which, when degraded, releases detectable products into the blood. Sphingosine-1-phosphate (S1P) is a cardiovascular biomarker involved in glycocalyx preservation, linked to placentation and preeclampsia development. The study aimed to test the hypothesis that plasma S1P is altered alongside glycocalyx degradation products in severe preeclampsia compared with controls.</p><p><strong>Methods: </strong>We included 121 females: 41 with severe preeclampsia requiring treatment in the intensive care unit, 40 with preeclampsia but no need of intensive care unit treatment, and 40 with normotensive pregnancies. Plasma levels of S1P and glycocalyx degradation products-hyaluronic acid, SDC-1 (syndecan-1), and HSPG2 (heparan sulfate proteoglycan-2)-were analyzed from blood samples taken within 27 hours postpartum.</p><p><strong>Results: </strong>Postpartum plasma S1P was significantly lower in the intensive care unit cohort compared with both preeclampsia controls and normotensive controls (<i>P</i><0.001). Hyaluronic acid and SDC-1 levels were elevated in the intensive care unit group versus normotensive controls (<i>P</i>=0.009 and <i>P</i>=0.023), while HSPG2 was lower (<i>P</i><0.001). Plasma S1P correlated with hyaluronic acid and blood pressure.</p><p><strong>Conclusion: </strong>Intensive care patients with severe preeclampsia have lower plasma S1P levels and higher concentrations of glycocalyx degradation products, indicating more pronounced endothelial damage. These findings suggest that S1P is associated with preeclampsia severity and may serve as a biomarker to assess vascular damage in this patient population. Further studies are needed to explore the potential role of S1P in long-term cardiovascular risk assessment for patients with preeclampsia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004614","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":"Adrenomedullin 2/Intermedin Exerts Cardioprotective Effects by Regulating Cardiomyocyte Mitochondrial Function.","authors":"Yunlu Zhao,Takayuki Sakurai,Akiko Kamiyoshi,Megumu Tanaka,Yuka Ichikawa-Shindo,Hisaka Kawate,Yorishige Matsuda,Yan Zhang,Qianqian Guo,Peixuan Li,Ken Hoshiyama,Marina Hayashi,Jiake Li,Takayuki Shindo","doi":"10.1161/hypertensionaha.124.23666","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.23666","url":null,"abstract":"BACKGROUNDAdrenomedullin 2 (AM2) plays critical roles in regulating blood pressure and fluid balance. However, the specific involvement of AM2 in cardiac hypertrophy has not been comprehensively elucidated, warranting further investigation into its molecular mechanisms and therapeutic implications.METHODSCardiac hypertrophy was induced in adult mice lacking AM2 (AM2-/-) using transverse aortic constriction surgery. Comprehensive cardiac morphology, function, histology, and transcriptome/metabolome analyses were conducted. Signal transduction underlying AM2 stimulation in the cardiomyocytes was explored.RESULTSThe absence of endogenous AM2 led to the development of severe heart failure after transverse aortic constriction surgery, which was characterized by alterations in the mitochondrial morphology and function associated with glycolysis and the tricarboxylic acid cycle in the heart and cardiomyocytes of transverse aortic constriction-operated AM2-/- mice. AM2 stimulation was associated with the receptor-modifying factor RAMP2 (receptor activity-modifying protein 2), which primarily transduces signals through the MAPK pathway and affects the expression of genes involved in glycolysis, β-oxidation, and oxidative phosphorylation. The administration of exogenous AM2 alleviated heart failure following transverse aortic constriction.CONCLUSIONSAM2 crucially regulates mitochondrial functions associated with the glycolysis and tricarboxylic acid cycles in the cardiomyocytes, thereby exerting a protective effect on the heart under pressure overload conditions.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"7 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988524","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":"Correction to: Circulating miRNAs and Machine Learning for Lateralizing Primary Aldosteronism.","authors":"","doi":"10.1161/hyp.0000000000000242","DOIUrl":"https://doi.org/10.1161/hyp.0000000000000242","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"22 1","pages":"e4"},"PeriodicalIF":8.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988526","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":"Equating Office and Ambulatory Blood Pressure.","authors":"Md Marufuzzaman Khan,Catherine Xue,Long Ngo,Stephen P Juraschek","doi":"10.1161/hypertensionaha.124.24219","DOIUrl":"https://doi.org/10.1161/hypertensionaha.124.24219","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"17 1","pages":"161-165"},"PeriodicalIF":8.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988525","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":"Intraoperative Blood Pressure Misclassification Due to Inaccuracy of Noninvasive Oscillometric Cuff-Measured Blood Pressure.","authors":"Danny Sungsoo Kim,Sohee Kwon,Alan C Bovik,Mia K Markey,Edward L Giovannucci,Maxime Cannesson","doi":"10.1161/hypertensionaha.123.22570","DOIUrl":"https://doi.org/10.1161/hypertensionaha.123.22570","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"49 1","pages":"e1-e3"},"PeriodicalIF":8.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988529","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}