Hypertension最新文献

{"title":"Aldosterone-Producing Lesions Harboring <i>ATP1A1</i> and <i>ATP2B3</i> Mutations: An International Multicenter Study.","authors":"Peeradon Vibhatavata, Yueting Liu, Madson Q Almeida, Laurence Amar, Irina Bancos, Stephanie Baron, Frederike Butz, Debbie L Cohen, Silas A Culver, Fabio Luiz Fernandes-Rosa, Augusto G Guimaraes, Amir H Hamrahian, Jinbo Hu, Markus Kroiss, James M Luther, Matthias F Oettle, Ismail Osman, Benjamin Pariente, Troy H Puar, Juilee Rege, Fumitoshi Satoh, Ute Scholl, Michael Stowasser, Yuta Tezuka, Aaron M Udager, Anand Vaidya, Desmaré van Rooyen, Heather Wachtel, Tracy A Williams, Vin-Cent Wu, Chun-Yi Wu, Maria-Christina Zennaro, William F Young, William E Rainey, Adina F Turcu","doi":"10.1161/HYPERTENSIONAHA.126.27798","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27798","url":null,"abstract":"<p><strong>Background: </strong>Somatic aldosterone-driver mutations are identified in >90% of patients with primary aldosteronism undergoing adrenalectomy, and they display distinct demographic clustering. <i>ATP1A1</i> and <i>ATP2B3</i> mutations, encoding the Na⁺/K⁺ ATPase α1 subunit and the Ca²⁺ ATPase 3, respectively, are relatively rare and are often grouped as <i>ATPase</i> mutations. Differences in their clinical and biochemical phenotypes remain understudied.</p><p><strong>Methods: </strong>This international collaboration of 16 centers included patients with primary aldosteronism harboring pathogenic variants in <i>ATP1A1</i> and <i>ATP2B3</i>. Clinical data were collected from medical records. Where available, we compared histopathologic features and steroid profiles (from peripheral and adrenal vein samples) by liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>We included 300 patients (mean age, 57±11 years; 85% men) with aldosterone-producing lesions harboring <i>ATP1A1</i> (204) and <i>ATP2B3</i> (96) mutations. Age and sex distributions were similar. <i>ATP2B3</i> mutations were associated with lower serum potassium, higher lateralization indices, and stronger contralateral suppression. Postoperative biochemical cure was achieved in 96% of patients with <i>ATP2B3</i> mutations versus 83% of those with <i>ATP1A1</i> mutations (<i>P</i>=0.02). Multiple CYP11B2-positive lesions were observed in 47% of <i>ATP1A1</i> versus 27% of <i>ATP2B3</i> cases (<i>P</i>=0.03). Baseline peripheral steroid profiling was available in 126 patients (84 with <i>ATP1A1</i> and 42 with <i>ATP2B3</i>) and showed higher aldosterone concentrations in the <i>ATP2B3</i> group (median [interquartile range], 31 ng/dL [20-43] versus 23 ng/dL [11-38]; <i>P</i>=0.03).</p><p><strong>Conclusions: </strong><i>ATP</i>ase mutations are most common in middle-aged men with lateralized primary aldosteronism. Compared with <i>ATP1A1</i>, <i>ATP2B3</i> mutations are associated with a more severe primary aldosteronism phenotype, stronger lateralization, and higher rates of single aldosterone-producing lesions and postoperative biochemical cure.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":""},"PeriodicalIF":9.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181527","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":"Inhibition of ROCK2 via KD025/Belumosudil Alleviates Hypertensive End-Organ Damage","authors":"Daniel J. Fehrenbach,C. Duncan Smart,Jean W. Wassenaar,Sharia Yasmin,Xinlan L. Li,Marisa N. Sepulveda,Ariane Imulinde Sugi,Hiroaki Shimokawa,Amanda C. Doran,Il-man Kim,Meena S. Madhur","doi":"10.1161/hypertensionaha.125.26418","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.26418","url":null,"abstract":"BACKGROUND: Despite achieving target blood pressure, hypertensive individuals have an elevated risk of cardiovascular disease, likely due to unresolved inflammation. Thus, adjunctive immune-modulating therapies are needed to protect patients with hypertension from end-organ damage. We previously showed that T helper 17 cells, which produce the proinflammatory cytokine IL (interleukin)-17A, contribute to hypertensive tissue injury. ROCK2 (Rho-associated coiled-coil–containing protein kinase 2) is a molecular switch governing T helper cell differentiation by promoting T helper 17 polarization and inhibiting T regulatory cell polarization. The present study tests whether T-cell–specific deletion of Rock2 or the Food and Drug Administration–approved ROCK2-specific inhibitor KD025/belumosudil protects against hypertension-associated end-organ damage. METHODS: T-cell–specific Rock2 knockout mice ( Rock2 fl/fl CD4 Cre+ ) and Rock2 fl/fl littermate controls were subjected to a 21-day deoxycorticosterone acetate–salt model of hypertension. In parallel, KD025/belumosudil treatment (50 mg/kg per day) starting after day 10 in wild-type mice was used to test the therapeutic potential of targeting ROCK2. Blood pressure, cardiac fibrosis, renal injury, and infiltration of immune cells were assessed. RESULTS: T-cell–specific Rock2 deletion in mice attenuated the hypertensive response in the deoxycorticosterone acetate–salt model and protected from cardiac and aortic fibrosis. KD025/belumosudil treatment did not reduce blood pressure but did decrease proinflammatory T helper 17 polarization in vivo and increased the cardiac regulatory T cells/T helper 17 ratio. Despite no blood pressure change, KD025 reduced cardiac and aortic fibrosis, improved echocardiographic and invasive hemodynamic indices, and attenuated albuminuria and renal T-cell infiltration. CONCLUSIONS: ROCK2 inhibition may serve as an adjunct immune-modulating therapy to mitigate the end-organ damage that occurs in the heart, vasculature, and kidney in hypertension.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"19 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088006","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":"Professor John Low Reid, OBE, DM, FRCP, FRSE, FMedSci.","authors":"Anna F Dominiczak, Christian Delles, George S Stergiou, Matthew Walters, Ian B Wilkinson, Anthony Heagerty","doi":"10.1161/HYPERTENSIONAHA.126.27702","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27702","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e27702"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759307","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":"Roles of Sirtuin-1 in the Prevention of Intracranial Aneurysm Rupture in Mice.","authors":"Hiroki Sato, Taichi Ikedo, Yushiro Take, Tetsuro Kimura, Takeshi Miyamoto, Daisuke Kudo, Redi Rahmani, Taichi Ishiguro, Hiroki Uchikawa, Takuma Maeda, Hitomi Sato, James Purcell, Jordan Morgan, Kyle Polen, Hiroki Kurita, Jinglu Ai, Satoru Eguchi, Michael T Lawton, Tomoki Hashimoto","doi":"10.1161/HYPERTENSIONAHA.125.26029","DOIUrl":"10.1161/HYPERTENSIONAHA.125.26029","url":null,"abstract":"<p><strong>Background: </strong>SIRT1 (sirtuin-1) regulates various cellular and metabolic processes in the vasculature. SIRT1 is an NAD⁺-dependent deacetylase that deacetylates transcription factors that control vascular inflammation and remodeling. Given that pathways regulated by SIRT1 are implicated in the pathophysiology of intracranial aneurysms, we hypothesized that activation and overexpression of SIRT1 prevent aneurysm rupture by suppressing vascular inflammation.</p><p><strong>Methods: </strong>Intracranial aneurysms were induced in mice by systemic hypertension and a single intracisternal injection of elastase. We analyzed the expression of SIRT1 in human and mouse aneurysms. We investigated the role of SIRT1 in aneurysm rupture using genetic overexpression of SIRT1 and cell-specific deletion in the endothelial, vascular smooth muscle, and myeloid lineages. We administered a SIRT1 activator and a SIRT1 inhibitor to assess the rupture rate and mRNA expression in cerebral arteries.</p><p><strong>Results: </strong>SIRT1 expression was significantly lower in intracranial aneurysm tissues than in control cerebral arteries in mice, with a similar trend in human aneurysms. Global overexpression of SIRT1 significantly decreased the rupture rate. Endothelial SIRT1 deletion increased the rupture rate, with no effect observed in other cell types. Inhibition of SIRT1 increased the rupture rate, whereas SIRT1 activation reduced the rupture rate and suppressed mRNA expression of proinflammatory cytokines in cerebral arteries.</p><p><strong>Conclusions: </strong>Our findings support a protective role of SIRT1 against intracranial aneurysm rupture in mice, with endothelial SIRT1 playing an important role in aneurysm stabilization. Pharmacological SIRT1 activation reduced aneurysm rupture and was associated with reduced vascular inflammation, providing a preclinical rationale for further investigation of SIRT1-related pathways.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e26029"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663739","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":"Hemodynamics and Renin Profiles of Renal Artery Variations in Hypertensive CKD.","authors":"Hongkun Ma, Kexin Jin, Xueqin Xu, Ri Ji, Qingbing Wang, Zijin Chen, Chongjian Wang, Zhiyu Wang, Pingyan Shen, Xiaoyi Ding, Zhiyuan Wu, Wen Zhang","doi":"10.1161/HYPERTENSIONAHA.126.27130","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27130","url":null,"abstract":"<p><strong>Background: </strong>The functional implications of renal artery variations-including accessory renal artery (ARA) and early branching-in hypertensive chronic kidney disease remain poorly understood.</p><p><strong>Methods: </strong>This prospective cohort study enrolled 38 patients with hypertensive chronic kidney disease and unilateral solitary renal artery variation (24 ARA, 14 early branching) undergoing pressure wire-based hemodynamic evaluation and selective segmental renal vein renin sampling; 35 patients completed 2-year follow-up.</p><p><strong>Results: </strong>Mean pressure gradient was higher in variant artery than in ipsilateral main (1.10±3.39 versus -0.15±2.21 mm Hg, <i>P</i>=0.04) and contralateral renal artery (versus -0.10±1.56 mm Hg, <i>P</i>=0.04) in the overall cohort, a difference limited to the ARA subgroup. Plasma renin activity was elevated in ARA-supplied segments compared with the ipsilateral main trunk (1.77±1.86 versus 1.24±1.40 ng/(mL·h), <i>P</i>=0.004) and contralateral artery-supplied segments (versus 1.24±1.37, <i>P</i>=0.002), whereas no significant difference was observed in the early branching subgroup. After multivariable adjustment, variant artery systolic pressure gradient was positively associated with variant-supplied segmental (β=0.41, <i>P</i>=0.02) and peripheral (β=0.37, <i>P</i>=0.04) plasma renin activity, angiotensin II, and nighttime mean arterial pressure. Peripheral aldosterone was associated with lower estimated glomerular filtration rate and higher urinary protein. All adjusted associations represent exploratory signals given limited sample size. Over 2 years, an intragroup estimated glomerular filtration rate decline was observed within the ARA subgroup (-5.2 mL/[min·1.73 m²]; <i>P</i>=0.02) while the early branching subgroup remained stable (<i>P</i>=0.47); however, the group-by-time interaction was not significant (<i>P</i>=0.06), indicating these preliminary trends require larger validation cohorts.</p><p><strong>Conclusions: </strong>Renal artery variations may alter intrarenal hemodynamics, with functional impairment and segmental renin hypersecretion observed primarily in ARA. This suggests a potential role for functional evaluation.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e27130"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808507","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":"Brief Commentary on Blood Pressure, Pulse Wave Velocity, and Body Composition in Children and Adolescents.","authors":"Mieczysław Litwin","doi":"10.1161/HYPERTENSIONAHA.126.27742","DOIUrl":"https://doi.org/10.1161/HYPERTENSIONAHA.126.27742","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"83 10","pages":"e27742"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982584","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":"CD38⁺ T-Cell Count Is an Immunologic Phenotype Associated With Blood Pressure.","authors":"Chuan Lin, Yajuan Xiao, Xin Zhou, Suhan Zhou, Reema Abdullah, Jianghua Chen, Fei Han, Pingping Ren, Liang Xiao","doi":"10.1161/HYPERTENSIONAHA.126.27403","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27403","url":null,"abstract":"<p><strong>Background: </strong>T lymphocytes play a crucial role in the development of hypertension and associated end-organ damage. CD38 is a well-established surface marker for T-cell activation. However, clinical evidence linking CD38⁺ T cells, or other specific T-cell subsets, with blood pressure (BP) changes remains limited. We therefore sought to determine whether CD38⁺ T-cell abundance correlates with BP and whether anti-CD38 therapy influences BP in humans and mice.</p><p><strong>Methods: </strong>We performed correlation analyses between peripheral immune cell counts and BP in 197 normotensive and 53 hypertensive subjects. The impact of CD38-targeted therapy on BP was evaluated in multiple myeloma patients (control, n=50; daratumumab, n=27). In addition, we used a murine model of angiotensin II-induced hypertension to characterize T-cell frequency and phenotype in the circulation and kidney by flow cytometry.</p><p><strong>Results: </strong>Circulating CD38⁺ T-cell abundance was inversely correlated with BP in both normotensive and hypertensive subjects. This finding was recapitulated in hypertensive mice, which also showed concomitant accumulation of CD38⁺ T cells in the kidney. In patients, daratumumab-induced depletion of CD38⁺ cells reduced systolic BP by ≈10 mm Hg for 4 to 6 weeks. This BP-lowering effect was similarly observed in hypertensive mice given an antimurine CD38 antibody.</p><p><strong>Conclusions: </strong>Our data identify circulating CD38⁺ T cells as a novel immunologic biomarker that inversely correlates with BP, potentially reflecting T-cell transmigration during BP elevation.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e27403"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764103","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":"Arterial Elasticity in Chinese Youth: References and the Role of Muscle.","authors":"Hongbo Dong, Yan Li, Minjun Li, Xiangjun Xie, Pei Xiao, Yanyan Li, Lina Lan, Jingfan Xiong, Jie Mi","doi":"10.1161/HYPERTENSIONAHA.126.27207","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27207","url":null,"abstract":"<p><strong>Background: </strong>Arterial elasticity, noninvasively assessed by carotid-femoral pulse wave velocity (cfPWV), is an important determinant of cardiovascular health, yet reference values are lacking for Chinese youth. Moreover, the interplay between adiposity, skeletal muscle mass, and blood pressure regarding cfPWV remains unclear.</p><p><strong>Methods: </strong>We analyzed 2077 Chinese children and adolescents aged 6 to 14 years from a cross-sectional survey. Among them, 1382 nonobese, normotensive, and metabolically healthy participants were selected as the reference population to derive sex-, age-, and height-specific cfPWV centiles, from which cfPWV <i>Z</i> scores were calculated in the overall population to examine potential correlates.</p><p><strong>Results: </strong>In the reference population, cfPWV increased with age and height in both sexes, with a steeper rise after the age of 10 years. In the overall population, higher fat mass index and systolic blood pressure were independently associated with higher cfPWV <i>Z</i> scores, whereas higher appendicular skeletal muscle mass index was associated with lower cfPWV <i>Z</i> scores in both boys (β=-0.123, <i>P</i>=0.018) and girls (β=-0.135, <i>P</i>=0.027). Although excess adiposity was associated with impaired arterial elasticity (odds ratio, 1.99 [95% CI, 1.06-3.74]) in boys with low-to-medium muscle mass, this association was attenuated among those with high muscle mass (odds ratio, 1.32 [95% CI, 0.65-2.65]). These patterns were not clearly observed in girls.</p><p><strong>Conclusions: </strong>This study establishes the first growth-specific cfPWV reference standards for Chinese youth. The favorable association of muscle mass with arterial elasticity suggests that muscle-building strategies could be considered alongside weight management in early pediatric cardiovascular prevention.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e27207"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619749","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":"Cautionary Data on Antihypertensives in Aortic Diseases.","authors":"Guan Fan, Alan Daugherty, Hong S Lu","doi":"10.1161/HYPERTENSIONAHA.126.27758","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27758","url":null,"abstract":"","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"83 10","pages":"e27758"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982567","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":"Chemogenetic Ca²⁺ Channel Mitigates Aortic Dissection and Antihypertensive Risk.","authors":"Xuan Wang, Xiao-Tian Li, Hao-Nan Chen, Hong-Li Zou, Jin Kuang, Yan-Ni Hu, Jin-Fu Peng, Chang-Ping Hu, Qing Wang, Mi Wang, Zheng Zhang","doi":"10.1161/HYPERTENSIONAHA.126.27008","DOIUrl":"10.1161/HYPERTENSIONAHA.126.27008","url":null,"abstract":"<p><strong>Background: </strong>Thoracic aortic dissection (TAD) is a highly lethal disease without effective drug therapy. Guidelines recommend control of risk factors, particularly of causal hypertension. Antihypertensive drugs are diverse in mechanisms of action, but no randomized controlled trials have been undertaken to evaluate their efficacy and safety, and guide rational drug selection for this disease.</p><p><strong>Methods: </strong>Antihypertensive drugs were evaluated in a 3-aminopropionitrile-induced mouse model of TAD. Pharmacovigilance analysis using the Food and Drug Administration Adverse Events Reporting System and Medical Information Mart for Intensive Care databases, along with a systematic meta-analysis of 32 studies, was performed to assess drug-associated risks in aortic diseases. Signaling pathways related to smooth muscle cell contractility, adhesion, and cytoskeleton stabilization were examined in human and mouse tissues. A chemogenetic mouse strain with smooth muscle cell-specific expression of the pharmacologically selective actuator module 4-serotonin type 3 receptor channel was generated to modulate Ca²⁺ signaling.</p><p><strong>Results: </strong>Here, we assessed 8 classes of antihypertensives in a mouse TAD disease model but unexpectedly observed that hydrochlorothiazide and minoxidil exacerbated the disease. Pharmacovigilance analysis linked diuretic use to an increased TAD-associated risk in patients. TAD pathogenesis and the harmful drug effects are attributable to blunted Ca²⁺-dependent smooth muscle cell contractility and adhesion. To this therapeutic end, we leveraged a chemogenetic Ca²⁺-permeable cation channel (pharmacologically selective actuator module 4-serotonin type 3 receptor) exclusively activated by the clinical drug varenicline. The humanized chemogenetic device boosted smooth muscle cell Ca²⁺ signaling, potentiated the Ca²⁺-dependent cellular processes, and protected against TAD and the aggravated phenotype induced by hydrochlorothiazide/minoxidil.</p><p><strong>Conclusions: </strong>This study calls for pharmacovigilance of certain antihypertensives in TAD, and suggests that pharmacologically selective actuator module 4-serotonin type 3 receptor, as a viable means of tuning Ca²⁺ signaling, holds translational potential for TAD therapy.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"e27008"},"PeriodicalIF":9.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663742","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}