Hypertension最新文献

{"title":"Cosyntropin-Stimulated Aldosterone Reserve of the Nondominant Adrenal Predicts Surgical Outcomes in Primary Aldosteronism.","authors":"Peeradon Vibhatavata,James J Shields,Juilee Rege,Aaron Udager,William E Rainey,Adina F Turcu","doi":"10.1161/hypertensionaha.125.24999","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.24999","url":null,"abstract":"BACKGROUNDAdrenal vein sampling (AVS) is commonly used to direct therapy of primary aldosteronism (PA). We hypothesized that cosyntropin stimulation during AVS exposes the reserve of aldosterone-producing cells in the nondominant adrenal gland and might predict postoperative outcomes.METHODSPatients with PA who underwent successful AVS before and after cosyntropin stimulation between January 2015 and December 2024 in a tertiary-referral center were included. The nondominant adrenal aldosterone reserve was assessed with (1) contralateral aldosterone reserve ratio (=aldosterone postcosyntropin-to-baseline ratio in the nondominant adrenal vein) and (2) lateralization index (LI) ratio (=LIpost-cosyntropin/LIbaseline). Lateralization was based on LI ≥4.RESULTSFour hundred thirty-four patients (57% men; mean age, 53±12 years) were included. AVS lateralized only at baseline in 52 (12%) patients, only after cosyntropin in 46 (11%), and in both protocols in 166 (38%); 170 (39%) patients had bilateral PA. PA severity decreased from cases lateralized in both protocols, to postcosyntropin only, baseline only, and consistently bilateral; conversely, the contralateral aldosterone reserve increased across these groups. The contralateral aldosterone reserve was higher in patients without PA cure and bilateral PA (median [interquartile range], 11.2 [5.0-23.5] and 17.9 [9.1-32.0], respectively, versus 4.9 [2.5-9.4] in those cured; P<0.01) and in Black individuals, those aged ≥45 years, and with CACNA1D mutations. Contralateral aldosterone reserve and postcosyntropin lateralization and contralateral suppression were predictive of residual PA, while baseline parameters were not.CONCLUSIONSCosyntropin stimulation during AVS unveils the aldosterone reserve in the nondominant adrenal gland, exposing the risk of residual disease after adrenalectomy.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"26 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769697","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":"Macrophage-Derived LCN2 Promotes Methamphetamine-Induced Pulmonary Hypertension.","authors":"Jie Zhou, Zhenzhen Xu, Dao-Bo Peng, Xiaoting Li, Sheng Chang, Ke Duan, Yating Jiang, Cihang Gu, Xiaojia Peng, Wei-Bing Xie","doi":"10.1161/HYPERTENSIONAHA.124.24548","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24548","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine (METH), a novel amphetamine-type psychostimulant, is recognized as a risk factor for pulmonary hypertension (PH). Macrophage activation is a key event in pulmonary vascular remodeling and PH progression, but the specific mechanisms of METH-induced PH (METH-PH) remain unclear.</p><p><strong>Methods: </strong>A METH-PH mouse model was constructed using wild-type and Lipocalin 2 (LCN2) knockout (LCN2^-/-) mice. The involvement and underlying mechanism of LCN2 in METH-PH formation were explored using a METH-PH mouse model and a coculture system of macrophages and pulmonary artery smooth muscle cells.</p><p><strong>Results: </strong>In this study, LCN2 was identified as a key regulator of perivascular inflammation and pulmonary vascular remodeling in PH. In the METH-PH mouse model, LCN2 expression was elevated in macrophages within lung tissues. Compared with wild-type mice, LCN2^-/- mice were protected from METH-PH, exhibiting reduced pulmonary vascular remodeling and right ventricular pressure. Mechanistically, LCN2 regulates IL-1β (interleukin-1β) production and secretion through NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome activation. In pulmonary artery smooth muscle cells, macrophage-derived LCN2 upregulates the expression of SLC7A11 (solute carrier family 7 member 11) and GPX4 (glutathione peroxidase 4), thereby reducing reactive oxygen species production and preventing ferroptosis.</p><p><strong>Conclusions: </strong>Our data revealed a novel mechanism linking LCN2 to macrophages, inflammatory responses, vascular remodeling, and intercellular interactions, indicating that LCN2 could serve as a therapeutic target for METH-induced PH.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1355-1367"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368818","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":"Does Aspirin Affect Extracellular Vesicles Involved in the Pathogenesis of Preeclampsia? A Systematic Review and Meta-Analysis.","authors":"Angel Nilesh D'Crus, Soumyalekshmi Nair, Jessica Jellins, Fabricio Da Silva Costa, Jon Hyett, Carlos Salomon","doi":"10.1161/HYPERTENSIONAHA.125.24826","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24826","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a challenging pregnancy disorder to treat, and current preventive measures are not always effective. Aspirin is prescribed as a preventive agent for pregnant women who are at high risk of developing preeclampsia although there is no definitive conclusion for its mechanism of action or efficacy. Extracellular vesicles (EVs) provide a picture of the physiological state of the cells from which they originate and have been implicated in both normal and pathological pregnancies. This study reviewed the potential effects of aspirin on EVs when prescribed for prevention of preeclampsia.</p><p><strong>Methods: </strong>The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to identify published studies from the CENTRAL, The Cochrane Library (Cochrane Central Register of Controlled Trials), MEDLINE (Medical Literature Analysis and Retrieval System online) on PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and Embase (Excerpta Medica Database) from inception to March 2024.</p><p><strong>Results: </strong>Sixty-three studies met the inclusion criteria and were grouped as studies on aspirin-mediated prevention of preeclampsia (n=31), studies on EVs in the pathogenesis of preeclampsia (n=28), and studies on the effects of aspirin on EVs in preeclampsia (n=4). Meta-analysis of randomized control trials showed that the odds of preeclampsia occurrence is 36% less likely in the aspirin treatment group (odds ratio, 0.64 [95% CI, 0.47-0.87]; <i>P</i><0.01). EVs are involved in the pathogenesis of preeclampsia, and aspirin effectively reduced the negative effects of EVs in both in vitro and in vivo studies.</p><p><strong>Conclusions: </strong>Aspirin has an inhibitory effect on EVs in preeclampsia. However, further studies are needed to understand and confirm the mechanisms involved.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1277-1291"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198889","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":"Degradation of nNOS in the PVN of Rats With Heart Failure: Role of CHIP.","authors":"Tapan A Patel, Kenichi Katsurada, Hong Zheng, Kaushik P Patel","doi":"10.1161/HYPERTENSIONAHA.125.24896","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24896","url":null,"abstract":"<p><strong>Background: </strong>One salient feature of congestive heart failure (CHF) is the exaggerated sympathetic drive. Reduced nNOS (neuronal nitric oxide synthase) within the paraventricular nucleus (PVN) is primarily responsible for the enhanced sympathetic tone in CHF. Here, we examined the role of CHIP (C-terminus of heat shock cognate protein 70-interacting protein) as a key regulator of nNOS in the PVN.</p><p><strong>Methods: </strong>CHF in rats was induced by left coronary artery ligation. Alterations in the expression of nNOS, CHIP, HSP70 (heat shock protein 70), and HSP90 (heat shock protein 90) in the PVN of CHF rats were evaluated by Western blot and immunofluorescence techniques. Neuronal NG108-15 cells were used to analyze the effect of CHIP overexpression (using the pCMV3-CHIP-GFP spark plasmid) on nNOS expression in vitro. CHIP overexpression was achieved by viral injections in the PVN of normal rats.</p><p><strong>Results: </strong>CHIP (50%) and HSP70 (33%) were significantly upregulated in the PVN of rats with CHF. Overexpression of CHIP in neuronal NG108-15 cells showed an ≈74% increase in CHIP with a concomitant decrease in nNOS expression (≈49%). Overexpression of CHIP significantly increased ubiquitination of nNOS (46%) in NG108-15 cells. Overexpression of CHIP in the PVN of normal control rats significantly reduced NO-mediated inhibition of renal sympathetic nerve activity, blood pressure, and heart rate.</p><p><strong>Conclusions: </strong>Overall, these studies identify overexpression of CHIP, which triggers ubiquitination and proteasomal degradation of nNOS in the PVN results in reduced inhibitory sympathetic tone in CHF.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1292-1302"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208379","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":"Altered Blood Pressure Reflexes in Women With Endometriosis.","authors":"Auni C Williams,Lacy M Alexander","doi":"10.1161/hypertensionaha.125.25089","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25089","url":null,"abstract":"BACKGROUNDEndometriosis is a risk factor for cardiovascular disease. COX (Cyclooxygenase) is upregulated in endometriotic lesions, potentially exaggerating pressor reflexes, a major risk factor for adverse cardiovascular events. The purpose of this study was to determine whether women with endometriosis demonstrate exaggerated pressor responses. We hypothesized that women with endometriosis would show exaggerated BP compared with healthy women during handgrip exercise and cold pressor testing (CPT).METHODSIn a single-blind, randomized, crossover design, women with (Endo ; n=11) and without (HC; n=9) endometriosis underwent a CPT and handgrip with postexercise ischemia following aspirin (a nonselective COX inhibitor; 650 mg) or placebo. Blood pressure was continuously monitored during baseline (5 minutes) and hand submersion (3 minutes; 4-8 °C) during CPT, and during baseline (5 minutes), 30% maximal voluntary contraction handgrip (2 minutes), and postexercise ischemia (3 minutes) for handgrip with postexercise ischemia.RESULTSWomen with endometriosis demonstrated attenuated pressor responses to CPT (∆MAP Endo 21±16 versus HC 34±20 mm Hg; P<0.01) and handgrip with postexercise ischemia (handgrip/postexercise ischemia: ΔMAP Endo=12±13/13±10 mm Hg, HC=24±14/20±8 mm Hg; P<0.01). There was no effect of aspirin on blood pressure response to either CPT or handgrip with postexercise ischemia.CONCLUSIONSCompared with age-matched HC, women with endometriosis demonstrate lower increases in blood pressure in response to cold exposure and exercise. Aspirin, a COX inhibitor, had no impact on these responses. Collectively, these results suggest that women with endometriosis demonstrate altered central integration and attenuated sympathetic outflow and end-organ responsiveness.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"135 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756061","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":"Calcium Aspirin Preeclampsia Early Prevention and Response (CASPER) Trial in Blantyre, Malawi: A Double-Blinded Cluster Randomized Trial.","authors":"Memory M Ngwira, Angela Makris, Renuka Shanmugalingam, John L Mbotwa, Josiah Mayani, Luis A Gadama, Annemarie Hennessy","doi":"10.1161/HYPERTENSIONAHA.125.24675","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24675","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia remains one of the major causes of maternal and neonatal mortality and morbidity, and yet it is uncertain whether aspirin combined with calcium would reduce the burden of preeclampsia in Malawian women, as elsewhere. This study assessed the efficacy of early low-dose aspirin in preventing in women given calcium to prevent preeclampsia/eclampsia in Blantyre, Malawi.</p><p><strong>Methods: </strong>This was a pragmatic, double-blind, cluster randomized controlled trial conducted in 4 urban health centers and Queen Elizabeth Central Hospital in Blantyre. A total of 306 women at high risk of preeclampsia were assigned to low-dose aspirin (150 mg/day) or placebo from 12 to 16 weeks until 34 weeks of gestation in clusters. All women were given calcium 1 g/day. The intention-to-treat analysis and adherence analysis were conducted with the primary end point of preeclampsia.</p><p><strong>Results: </strong>A total of 39 women were lost to follow-up, and 1 withdrew consent. Data for 266 women were available for analysis. Overall, preeclampsia occurred in 15.8% (42/266) and eclampsia in 2.3% (6/266) of all women. There was no statistically significant difference in the rate of preeclampsia between the low-dose aspirin group 19.3% (26/135) and placebo group (12.2% 16/131; adjusted odds ratio, 1.16 [95% CI, 0.41-3.41]; <i>P</i>=0.781). No statistically significant difference was observed in the secondary maternal and neonatal outcomes. The overall adherence was 69%.</p><p><strong>Conclusions: </strong>In high-risk women treated with calcium, additional low-dose aspirin resulted in no difference in the rate of preeclampsia, cesarean section rates, or important neonatal outcomes in Malawi.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1316-1325"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247658","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":"Hypertension in Pregnancy Linked to Cerebral Small Vessel Disease 15 Years Later.","authors":"Rowina F Hussainali, Maria C Adank, Sander Lamballais, Meike W Vernooij, M Arfan Ikram, Eric A P Steegers, Eliza C Miller, Sarah Schalekamp-Timmermans","doi":"10.1161/HYPERTENSIONAHA.124.24544","DOIUrl":"10.1161/HYPERTENSIONAHA.124.24544","url":null,"abstract":"<p><strong>Background: </strong>Substantial evidence suggests an association between hypertensive disorders of pregnancy and long-term cerebrovascular health. We aimed to determine the associations between hypertensive disorders of pregnancy and markers of cerebral small vessel disease 15 years after pregnancy.</p><p><strong>Methods: </strong>This was a nested cohort study embedded in a population-based prospective cohort followed from early pregnancy. We included 538 women, 445 (82.8%) with normotensive index pregnancies, and 93 (17.2%) with hypertensive disorders in the index pregnancy. Fifteen years after the index pregnancy (median, 14.6 years; 90% range, 14.0-15.7 years), women underwent magnetic resonance imaging to assess brain tissue and white matter hyperintensity volume, lacunar infarcts, and cerebral microhemorrhages as markers of cerebral small vessel disease.</p><p><strong>Results: </strong>Women with prior hypertensive disorders of pregnancy had higher white matter hyperintensity volume compared with women with previous normotensive pregnancy (adjusted β, 0.32 [95% CI, 0.08-0.56]). This association was driven by women with gestational hypertension, who had higher white matter hyperintensity volume compared with women with previous normotensive pregnancy (adjusted β, 0.39 [95% CI, 0.10-0.67]). The effect was larger in those with gestational hypertension who developed chronic hypertension after the index pregnancy. No differences were found in infarcts or cerebral microhemorrhages.</p><p><strong>Conclusions: </strong>In a prospective cohort of midlife Dutch women, those with a history of hypertensive disorders of pregnancy, particularly gestational hypertension, showed some signs of cerebral small vessel disease, compared with those with normotensive pregnancies. These results support epidemiological data suggesting that not only preeclampsia but also gestational hypertension is associated with long-term cerebrovascular risk.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1326-1335"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247659","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":"Are Diuretics a Clandestine Risk Factor for Patients With Treatment-Resistant Hypertension?","authors":"Bertram Pitt, Christopher S Wilcox","doi":"10.1161/HYPERTENSIONAHA.125.24871","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24871","url":null,"abstract":"<p><p>The control of blood pressure in patients with treatment-resistant hypertension is paramount and requires the use of thiazide or loop diuretics to enhance renal salt excretion and reduce expanded body fluid volumes. However, the use of diuretics in patients with treatment-resistant hypertension without suppressing the production of aldosterone and MR (mineralocorticosteroid receptor) activation and signaling may not be sufficient to prevent the development of heart failure and excessive cardiovascular mortality and the progression of chronic kidney disease. This review examines the evidence that diuretic therapy for treatment-resistant hypertension may constitute a risk factor for preventable cardiovascular and renal disease progression that is concealed by the strong offsetting effects of a fall in blood pressure. To gain the full benefits of diuretic therapy in treatment-resistant hypertension may require the earlier prescription of MR antagonists coincident with diuretics rather than delaying their use to fourth-line agents in those who remain uncontrolled. This will require testing in appropriate clinical trials.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1271-1276"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173738","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":"L-Citrulline Improves IGF-1 Signaling Pathway in Preeclampsia via Polyamines.","authors":"Andy W C Man, Joscha Steetskamp, Josche van der Ven, Gisela Reifenberg, Annette Hasenburg, Andreas Daiber, Ning Xia, Huige Li","doi":"10.1161/HYPERTENSIONAHA.125.24785","DOIUrl":"10.1161/HYPERTENSIONAHA.125.24785","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is a severe pregnancy complication with no effective pharmacological therapy available. We previously demonstrated that L-citrulline supplementation improves preeclampsia phenotypes in Dahl salt-sensitive rats, an animal model of superimposed preeclampsia. This study aimed to investigate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>Pregnant Dahl salt-sensitive rats were treated with L-citrulline. In addition, patients with preeclampsia were recruited to donate placenta and serum samples.</p><p><strong>Results: </strong>In patients with preeclampsia, the placental IGF-1 (insulin-like growth factor 1) expression was significantly reduced compared with healthy pregnancy, associated with a downregulation of ZEB1 (zinc finger E-box binding homeobox 1) and an upregulation of miR-486-5p and miR-210. L-citrulline supplementation in preeclampsia rats significantly increased the placental expression of IGF-1 and ZEB1 and reduced the expression of miR-486-5p and miR-210. Total serum polyamine level was reduced in patients with preeclampsia and pregnant Dahl salt-sensitive rats, while L-citrulline treatment maintained the serum polyamine level in Dahl salt-sensitive rats during pregnancy. Placental IGF-1 expression was positively correlated to serum polyamine levels. Moreover, both L-citrulline and polyamines normalized the expression of IGF-1 and some antiangiogenic markers in cultured human placental vascular endothelial cells treated with preeclampsia serum. Results from IGF-1 siRNA experiments indicate that part of the L-citrulline effects on gene expression was dependent on IGF-1.</p><p><strong>Conclusions: </strong>L-citrulline supplementation improves the IGF-1 signaling pathway in preeclampsia, at least partly, via polyamine production. Maternal supplementation with L-citrulline or polyamine may represent a safe and effective therapeutic strategy for preeclampsia.</p>","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":" ","pages":"1303-1315"},"PeriodicalIF":6.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198890","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":"Epigenetic Histone β-Hydroxybutyrylation Contributes to Renoprotection by β-Hydroxybutyrate in the Dahl Rat.","authors":"Juthika Mandal,Sachin Aryal,Ishan Manandhar,Saroj Chakraborty,Xue Mei,Beng San Yeoh,Blair Mell,Andrew Kleinhenz,Ramakumar Tummala,Tao Yang,Piu Saha,William T Gunning,Matam Vijay-Kumar,Venkatesha Basrur,Ivana de la Serna,Bina Joe","doi":"10.1161/hypertensionaha.125.25251","DOIUrl":"https://doi.org/10.1161/hypertensionaha.125.25251","url":null,"abstract":"BACKGROUNDPreviously, we demonstrated that the ketone body, β-hydroxybutyrate, is a potent antihypertensive and reno-protective metabolite in Dahl Salt-Sensitive rats. However, the mechanism by which β-hydroxybutyrate confers these beneficial effects is understudied. Here we focused on determining whether the reno-protective effect of β-hydroxybutyrate is due to its known ability to epigenetically remodel chromatin via histone β-hydroxybutyrylation.METHODSWe used the same animal protocol previously used for the discovery of the reno-protective effect of β-hydroxybutyrate. Briefly, postweaning, male and female Dahl Salt-Sensitive rats were split into 2 groups and supplemented with or without 1,3-butanediol for 6 weeks. At euthanasia, circulating β-hydroxybutyrate was quantitated. Renal homogenates were examined for histone 3 lysine 9 β-hydroxybutyrylation, chromatin occupancy, transcriptomic and proteomic profiles with validations.RESULTSRats supplemented with 1,3-butanediol had higher circulating β-hydroxybutyrate, renal histone β-hydroxybutyrylation, and significant remodeling of chromatin. Notably, regions of the genome associated with lipid catabolism were predominantly in an open chromatin configuration, leading to active transcription and translation. The most highly upregulated gene actively transcribed and translated was Hmgcs2 (3-hydroxy-3-methylglutaryl CoA ssynthase 2), a gene responsible for the biosynthesis of β-hydroxybutyrate in mitochondria. In contrast, regions with more compact chromatin structures contained immune function genes, Ptprc (protein tyrosine phosphatase receptor type C) and Lcp1 (lymphocyte cytosolic protein 1), which were suppressed.CONCLUSIONSThese results reveal that renal epigenetic histone β-hydroxybutyrylation is a novel mechanism by which transcriptional regulation of both energy metabolism and immune function occur concomitantly and contribute to renoprotection in the hypertensive Dahl rat.","PeriodicalId":13042,"journal":{"name":"Hypertension","volume":"128 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720174","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}