Hypertension最新文献

{"title":"Baroreflex Sensitivity and Long-Term Dementia Risk in Older Adults.","authors":"Yuan Ma, Yiwen Zhang, Rikuta Hamaya, Berend E Westerhof, Hossam A Shaltout, Maryam Kavousi, Francesco Mattace-Raso, Albert Hofman, Frank J Wolters, Lewis A Lipsitz, M Arfan Ikram","doi":"10.1161/HYPERTENSIONAHA.124.24001","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24001","url":null,"abstract":"<p><strong>Background: </strong>Increased blood pressure (BP) variability is linked to dementia risk, but the relationship between baroreflex sensitivity (BRS), a fundamental mechanism for maintaining stable BP, and dementia risk is undetermined.</p><p><strong>Methods: </strong>We tested the hypothesis that impaired BRS is associated with increased dementia risk in 1819 older adults (63% women; age, 71.0±6.3 years) from the community-based Rotterdam Study. Cardiac BRS was determined from a 5-minute beat-to-beat BP recording at supine rest between 1997 and 1999. Cardiac BRS measures the correlation between changes in consecutive beat-to-beat systolic BP and subsequent responses in heartbeat intervals, with a higher value indicating better BRS. The primary outcome was incident dementia ascertained from baseline through January 1, 2020; the secondary outcome was all-cause mortality.</p><p><strong>Results: </strong>During a median follow-up of 14.8 years, 421 participants developed dementia. The association of cardiac BRS with dementia risk differed by antihypertensive medication use (<i>P</i>_interaction=0.03) and was only observed in participants not taking antihypertensives. Specifically, in those not taking antihypertensive medication, reduced BRS was associated with a higher risk of dementia (adjusted hazard ratio comparing bottom versus top quintiles, 1.60 [95% CI, 1.07-2.40]; <i>P</i>_trend=0.02). Reduced BRS was also associated with an increased risk of death (corresponding hazard ratio, 1.76 [95% CI, 1.32-2.35]). The association remained after adjusting for average BP and BP variability.</p><p><strong>Conclusions: </strong>Impaired BRS partly explains hypertension-related brain damage and excessive dementia risk beyond conventional BP measures, making it a potential novel biomarker for the early detection and prevention of dementia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"347-356"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817916","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":"Racism and Postpartum Blood Pressure in a Multiethnic Prospective Cohort.","authors":"Teresa Janevic, Frances M Howell, Micki Burdick, Sarah Nowlin, Sheela Maru, Natalie Boychuk, Oluwadamilola Oshewa, Maria Monterroso, Katharine McCarthy, Daniel A Gundersen, Alva Rodriguez, Cecilia Katzenstein, Regina Longley, Kellee White Whilby, Alison Lee, Camila Cabrera, Jennifer Lewey, Elizabeth A Howell, Lisa D Levine","doi":"10.1161/HYPERTENSIONAHA.124.23772","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23772","url":null,"abstract":"<p><strong>Background: </strong>Postpartum hypertension is a key factor in racial-ethnic inequities in maternal mortality. Emerging evidence suggests that experiences of racism, both structural and interpersonal, may contribute to disparities. We examined associations between gendered racial microaggressions (GRMs) during obstetric care with postpartum blood pressure (BP).</p><p><strong>Methods: </strong>We conducted a prospective postpartum cohort of 373 Asian, Black, and Hispanic people in New York City and Philadelphia. At delivery, we administered the GRM in obstetrics scale. We measured BP for 3 months using text-based monitoring. We estimated place-based structural racism with the Structural Racism Effect Index. We used mixed models to estimate associations between GRM and mean postpartum systolic BP and diastolic BP. We adjusted for race-ethnicity, education, body mass index, chronic hypertension (diagnosed at <20 weeks of gestation), age, and the Structural Racism Effect Index. We examined effect modification by hypertensive disorder of pregnancy and place-based structural racism.</p><p><strong>Results: </strong>A total of 4.6% of participants had chronic hypertension, 20.9% had pregnancy hypertension, and 13.4% had preeclampsia, comprising a hypertensive disorder of pregnancy subgroup (n=117). A total of 37.5% of participants experienced ≥1 GRM. Participants who experienced ≥1 GRM versus none had 1.88 mm Hg higher systolic BP from days 1 to 10 (95% CI, -0.19 to 3.95) and 2.19 mm Hg higher systolic BP from days 11 to 85 (95% CI, 0.17-4.22). Associations followed a similar pattern for diastolic BP and were stronger among the hypertensive disorder of pregnancy subgroup. Participants experiencing GRM and a high Structural Racism Effect Index had systolic BP 7.55 mm Hg (95% CI, 3.41-11.69) and diastolic BP 6.03 mm Hg (95% CI, 2.66-9.41) higher than those with neither.</p><p><strong>Conclusions: </strong>Structural racism and interpersonal racism are associated with increased postpartum BP, potentially contributing to inequities in postpartum morbidity and mortality and lifecourse cardiovascular disease.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"206-215"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948142","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":"Cardiac cGMP Regulation and Therapeutic Applications.","authors":"Sumita Mishra, Vivek Chander, David A Kass","doi":"10.1161/HYPERTENSIONAHA.124.21709","DOIUrl":"10.1161/HYPERTENSIONAHA.124.21709","url":null,"abstract":"<p><p>cGMP plays a central role in cardiovascular regulation in health and disease. It is synthesized by NO or natriuretic peptide activated cyclases and hydrolyzed to 5'GMP by select members of the PDEs (phosphodiesterase) superfamily. The primary downstream effector is cGMP-dependent protein kinase, primarily cGK-1a (cyclic GMP-dependent protein kinase 1 alpha) also known as protein kinase G 1a in the heart and vasculature. cGMP signaling is controlled in intracellular nanodomains to regulate myocyte growth, survival, metabolism, protein homeostasis, G-protein-coupled receptor signaling, and other critical functions. The vascular effects of cGMP signaling have been dominated by its lowering of smooth muscle tone, but other cellular processes are also engaged. Localization of cyclases and corresponding PDEs within intracellular domains, along with their varying expression across different cell types, adds multiorgan complexity to cGMP signaling. This diversity can be leveraged therapeutically by targeting selective pathway components to impact some but not other cGMP signaling effects. Here, we review the generation and regulation of cGMP by PDEs and cyclases, focusing mainly on their role in cardiac physiology and pathophysiology. Current therapeutic uses of cGMP modulation and ongoing trials testing new potential applications are discussed.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"185-196"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806905","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":"Ang-(1-7) and ET-1 Interplay Through Mas and ET_B Receptor Interaction Defines a Novel Vasoprotective Mechanism.","authors":"Augusto C Montezano, Jithin Kuriakose, Katie Y Hood, Yuan Yan Sin, Livia L Camargo, Yoon Namkung, Carlos H Castro, Robson A Santos, Rheure Alves-Lopes, Gonzalo Tejeda, Patricia Passaglia, Sehrish Basheer, Emily Gallen, Jane E Findlay, Fazli R Awan, Stéphane A Laporte, Margaret R MacLean, George S Baillie, Rhian M Touyz","doi":"10.1161/HYPERTENSIONAHA.124.22693","DOIUrl":"10.1161/HYPERTENSIONAHA.124.22693","url":null,"abstract":"<p><strong>Background: </strong>Ang-(1-7) (angiotensin (1-7)) via MasR (Mas receptor) opposes vaso-injurious actions of Ang II (angiotensin II) as shown in models of pulmonary hypertension. The underlying mechanisms remain unclear. We hypothesized cross talk between Ang-(1-7) and the protective arm of the ET-1 (endothelin-1) system involving MasR and ET_BR (endothelin receptor type B).</p><p><strong>Methods: </strong>To address this, we studied multiple models: in vivo, in a mouse model of ET-1-associated vascular injury (hypoxia-induced pulmonary hypertension); ex vivo, in isolated mouse arteries; and in vitro, in human endothelial cells.</p><p><strong>Results: </strong>Pulmonary hypertension mice exhibited pulmonary vascular remodeling, endothelial dysfunction, and ET-1-induced hypercontractility. Ang-(1-7) treatment (14 days) ameliorated these effects and increased the expression of vascular ET_BR. In human endothelial cells, Ang-(1-7)-induced activation of eNOS (endothelial NO synthase)/NO was attenuated by A779 (MasR antagonist) and BQ788 (ET_BR antagonist). A779 inhibited ET-1-induced signaling. Coimmunoprecipitation and peptide array experiments demonstrated the interaction between MasR and ET_BR. Binding sites for ET_BR were mapped to MasR (amino acids 290-314). Binding sites for MasR on ET_BR were identified (amino acids 176-200). Peptides that disrupt MasR:ET_BR prevented Ang-(1-7) and ET-1 signaling. Using high-throughput screening, we identified compounds that enhance MasR:ET_BR interaction, which we termed enhancers. Enhancers increased Ang-(1-7)-induced eNOS activity, NO production, and Ang-(1-7)-mediated vasorelaxation, and reduced contractile responses.</p><p><strong>Conclusions: </strong>We identify cross talk between Ang-(1-7) and ET-1 through MasR:ET_BR interaction as a novel network that is vasoprotective. Promoting coactivity between these systems amplifies Ang-(1-7) signaling, increases ET-1/ET_BR-mediated vascular actions, and attenuates the injurious effects of ET-1. Enhancing Ang-(1-7)/MasR:ET-1/ET_BR signaling may have therapeutic potential in conditions associated with vascular damage.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"267-281"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780202","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":"Caregiving and Hypertension in Younger Black Women: The Jackson Heart Study.","authors":"Milla E Arabadjian, Yiwei Li, Byron C Jaeger, Calvin L Colvin, Jolaade Kalinowski, Miriam A Miles, Lenette M Jones, Jacquelyn Y Taylor, Kenneth R Butler, Paul Muntner, Tanya M Spruill","doi":"10.1161/HYPERTENSIONAHA.124.23721","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23721","url":null,"abstract":"<p><strong>Background: </strong>Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults.</p><p><strong>Methods: </strong>We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004). Caregiving stress over the past 12 months was assessed via a single item in the global perceived stress scale. Caregiving for a high-needs dependent status was assessed via a question on hours per week spent caregiving for children (≤5 years or disabled) or older adults. Incident hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-report of taking antihypertensive medication at follow-up exams in 2005 to 2008 and 2009 to 2013.</p><p><strong>Results: </strong>Over a median follow-up of 7.4 years, 43.5% of participants developed hypertension. Participants with moderate/high versus no/low caregiving stress had a higher incidence of hypertension (51.7% versus 40.6%). Higher caregiving stress was associated with incident hypertension after adjustment for sociodemographic and clinical factors, health behaviors, and depressive symptoms (hazard ratio, 1.39 [95% CI, 1.01-1.94]). Being a caregiver for a high-needs dependent was not associated with incident hypertension (adjusted hazard ratio, 0.88 [95% CI, 0.64-1.21]).</p><p><strong>Conclusions: </strong>Higher caregiving stress among reproductive-age Black women was associated with incident hypertension. Hypertension prevention approaches for this high-risk population may include caregiving stress management strategies.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"232-240"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728107","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":"ATP2A3 in Primary Aldosteronism: Machine Learning-Based Discovery and Functional Validation.","authors":"Zhuolun Sun, Elisabeth Kemter, Yingxian Pang, Martin Bidlingmaier, Eckhard Wolf, Martin Reincke, Tracy Ann Williams","doi":"10.1161/HYPERTENSIONAHA.124.23817","DOIUrl":"10.1161/HYPERTENSIONAHA.124.23817","url":null,"abstract":"<p><strong>Background: </strong>Aldosterone-producing adenomas (APAs) are a common cause of primary aldosteronism that can lead to cardiovascular complications if left untreated. Machine learning-based bioinformatics approaches have emerged as powerful tools for identifying potential disease markers, gaining widespread recognition in biomedical research. We aimed to use machine learning to discover novel biomarkers of APAs to identify new pathophysiological mechanisms.</p><p><strong>Methods: </strong>We applied 2 machine learning algorithms to published RNA sequencing data to identify APA feature genes. Validation was performed using APA tissue samples, spatial transcriptomics, pig adrenal glands, and in vitro assays in a human adrenocortical cell line.</p><p><strong>Results: </strong>Machine learning identified <i>ATP2A3</i> as a key feature gene in APA, and its upregulation in APAs compared with the adjacent cortex was confirmed by spatial transcriptomics. In human adrenocortical cells, angiotensin II treatment increased <i>ATP2A3</i> gene expression 9.15-fold. Silencing <i>ATP2A3</i> decreased basal <i>CYP11B2</i> expression and aldosterone secretion by 3.51-fold and 1.46-fold, respectively, and by 1.77-fold and 1.94-fold under angiotensin II stimulation. Dietary sodium restriction in pigs significantly increased <i>ATP2A3</i> mRNA and protein levels. Spatial transcriptomics showed that APA cells exhibited higher <i>ATP2A3</i> gene expression compared with all other adrenal cell types. The suppressive effect of <i>ATP2A3</i> silencing on <i>CYP11B2</i> expression was further enhanced by Ca²⁺ inhibitors.</p><p><strong>Conclusions: </strong>The <i>ATP2A3</i> gene is highly expressed in APA and is a key regulator of <i>CYP11B2</i> expression and aldosterone production.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"319-332"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768563","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 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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}