Circulation research最新文献

{"title":"Arterial NALCN Knockdown Ameliorates Mineralocorticoid-Induced Hypertension and Arterial Overcontractility.","authors":"Hyeryeong Lee, Solah Park, Dong Jun Sung, Jin Ryeol An, Mi Seon Seo, Hyun Ju Noh, Jueng Soo You, Sung Hea Kim, Hana Cho, Bokyung Kim, Sang Woong Park, Young Min Bae","doi":"10.1161/CIRCRESAHA.124.325058","DOIUrl":"10.1161/CIRCRESAHA.124.325058","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"321-324"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945697","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":"Remote Ischemic Conditioning Attenuates Transneuronal Degeneration and Promotes Stroke Recovery via CD36-Mediated Efferocytosis.","authors":"Hyunwoo Ju, Il-Doo Kim, Ina Pavlova, Shang Mu, Keun Woo Park, Joseph Minkler, Ahmed Madkoor, Wei Wang, Xiaoman Wang, Zhuhao Wu, Jiwon Yang, Maria Febbraio, John W Cave, Sunghee Cho","doi":"10.1161/CIRCRESAHA.124.325428","DOIUrl":"10.1161/CIRCRESAHA.124.325428","url":null,"abstract":"<p><strong>Background: </strong>Remote ischemic conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest an inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood, which enhance long-term functional recovery in experimental cerebral ischemia.</p><p><strong>Methods: </strong>Naive mice or mice subjected to transient ischemic stroke were randomly selected to receive sham conditioning or RIC in the hindlimb at 2 hours post-stroke. At 3 days post-stroke, monocyte composition in the blood was analyzed, and brain tissue was examined for monocyte-derived macrophage (Mφ), levels of efferocytosis, and CD36 expression. Mouse with a specific deletion of CD36 in monocytes/Mφs was used to establish the role of CD36 in RIC-mediated modulation of efferocytosis, transneuronal degeneration, and recovery following stroke.</p><p><strong>Results: </strong>RIC applied 2 hours after stroke increased the entry of monocytes into the injured brain. In the postischemic brain, Mφ had increased levels of CD36 expression and efferocytosis. These changes in brain Mφ were derived from RIC-induced changes in circulating monocytes. In the blood, RIC increased CD36 expression in circulating monocytes and shifted monocytes to a proinflammatory LY6C^High state. Conditional deletion of CD36 in Mφ abrogated the RIC-induced monocyte shift in the blood and efferocytosis in the brain. During the recovery phase of stroke, RIC rescued the loss of the volume and of tyrosine hydroxylase+ neurons in substantia nigra and behavioral deficits in wild-type mice but not in mice with a specific deletion of CD36 in monocytes/Mφs.</p><p><strong>Conclusions: </strong>RIC induces a shift in monocytes to a proinflammatory state with elevated CD36 levels, and this is associated with CD36-dependent efferocytosis in Mφs that rescues delayed transneuronal degeneration in the postischemic brain and promotes stroke recovery. Together, these findings provide novel insight into our mechanistic understanding of how RIC improves poststroke recovery.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064064","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":"X-Chromosome-Linked miRNAs Regulate Sex Differences in Cardiac Physiology.","authors":"James I Emerson, Wei Shi, Jose Paredes-Larios, William G Walker, Josiah E Hutton, Ileana M Cristea, William F Marzluff, Frank L Conlon","doi":"10.1161/CIRCRESAHA.124.325447","DOIUrl":"10.1161/CIRCRESAHA.124.325447","url":null,"abstract":"<p><strong>Background: </strong>Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states.</p><p><strong>Methods: </strong>We identified microRNAs (miRNAs/miR) with sex-differential expression in mouse hearts.</p><p><strong>Results: </strong>Four conserved miRNAs are present in a single locus on the X-chromosome and are expressed at higher levels in females than males. We show miRNA, miR-871, is responsible for decreased expression of the protein SRL (sarcalumenin) in females. SRL is involved in calcium signaling, and we show it contributes to differences in electrophysiology between males and females. miR-871 overexpression mimics the effects of the cardiac physiology of conditional cardiomyocyte-specific Srl-null mice. Inhibiting miR-871 with an antagomir in females shortened ventricular repolarization. The human orthologue of miR-871, miR-888, coevolved with the SRL 3' untranslated region and regulates human SRL.</p><p><strong>Conclusions: </strong>These data highlight the importance of sex-differential miRNA mechanisms in mediating sex-specific functions and their potential relevance to human cardiac diseases.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"258-275"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945695","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":"Collagen Pyridinoline Cross-Links Are Absent in Reversible Myocardial Fibrosis.","authors":"Eman Akam-Baxter, Sterling J Ridley, Brianna F Moon, Peter Caravan, David E Sosnovik","doi":"10.1161/CIRCRESAHA.124.325406","DOIUrl":"10.1161/CIRCRESAHA.124.325406","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"315-317"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881368","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":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000708","DOIUrl":"https://doi.org/10.1161/RES.0000000000000708","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 3","pages":"255-257"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064083","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":"Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.","authors":"Zachary A Kohutek, Heather L Caslin, Daniel J Fehrenbach, J Brett Heimlich, Jonathan D Brown, Meena S Madhur, P Brent Ferrell, Amanda C Doran","doi":"10.1161/CIRCRESAHA.124.323778","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.323778","url":null,"abstract":"<p><p>Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis. Under normal conditions, this niche ensures a return to immune homeostasis after acute stress. However, in the setting of inflammatory conditions such as those seen in cardiometabolic diseases, it becomes dysregulated, leading to enhanced myelopoiesis and immune activation. This review explores the reciprocal relationship between the bone marrow niche and cardiometabolic diseases, highlighting how alterations in the niche contribute to disease development and progression. The niche regulates HSCs through complex interactions with stromal cells, endothelial cells, and signaling molecules. However, in the setting of chronic diseases such as hypertension, atherosclerosis, and diabetes, inflammatory signals disrupt the balance between HSC self-renewal and differentiation, promoting the excessive production of proinflammatory myeloid cells that exacerbate the disease. Key mechanisms discussed include the effects of hyperlipidemia, hyperglycemia, and sympathetic nervous system activation on HSC proliferation and differentiation. Furthermore, the review emphasizes the role of epigenetic modifications and metabolic reprogramming in creating trained immunity, a phenomenon whereby HSCs acquire long-term proinflammatory characteristics that sustain disease states. Finally, we explore therapeutic strategies aimed at targeting the bone marrow niche to mitigate chronic inflammation and its sequelae. Novel interventions that modulate hematopoiesis and restore niche homeostasis hold promise for the treatment of cardiometabolic diseases. By interrupting the vicious cycle of inflammation and marrow dysregulation, such therapies may offer new avenues for reducing cardiovascular risk and improving patient outcomes.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 3","pages":"325-353"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064068","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":"Vps4a Mediates a Unified Membrane Repair Machinery to Attenuate Ischemia/Reperfusion Injury.","authors":"Xiaozhi Huang, Jiayin Zhang, Chen Xu, Ranran Cao, Peijun Jiang, Xue Ji, Wenyi Wang, Zhishan Huang, Peidong Han","doi":"10.1161/CIRCRESAHA.124.325290","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325290","url":null,"abstract":"<p><strong>Background: </strong>Cardiac ischemia/reperfusion disrupts plasma membrane integrity and induces various types of programmed cell death. The ESCRT (endosomal sorting complex required for transport) proteins, particularly AAA-ATPase Vps4a (vacuolar protein sorting 4a), play an essential role in the surveillance of membrane integrity. However, the role of ESCRT proteins in the context of cardiac injury remains unclear.</p><p><strong>Methods: </strong>We simultaneously visualized the formation of membrane blebs and the subcellular translocation of Vps4a during a variety of cell death programs in primary cardiomyocytes. <i>Vps4a</i> cardiomyocyte-specific knockout and overexpression mice were generated and characterized. In vivo and ex vivo surgeries were performed to determine the effects of altered Vps4a expression levels on plasma membrane repair and cell survival. Given the role of Ripk3 (receptor-interacting kinase 3)-mediated pore formation in regulating cell membrane integrity, hearts from <i>Ripk3</i> and <i>Vps4a</i> double-knockout mice were examined. The sequential recruitment of upstream ESCRT components that promote the translocation of Vps4a to injured sites was also assessed using genetic gain- and loss-of-function approaches. Finally, we overexpressed a mutated form of Vps4a with defective ATPase activity and investigated its function during cardiomyocyte membrane repair.</p><p><strong>Results: </strong>Ischemia/reperfusion stimulation or forced induction of apoptosis, necroptosis, and pyroptosis in primary cardiomyocytes leads to membrane blebbing and the exposure of phosphatidylserine to the extracellular space. In response to injury, Vps4a promptly translocates to injured sites to reseal damaged membranes. <i>Vps4a</i> gain- and loss-of-function in the postnatal stage minimally affects cardiac structure formation and function. However, in the context of ischemia/reperfusion stimulation, overexpression of <i>Vps4a</i> protects cardiomyocytes against injury, whereas <i>Vps4a</i>-deficient hearts are more susceptible to cell damage. Additionally, <i>Ripk3</i> deletion abrogates the detrimental effects of <i>Vps4a</i> deficiency during ischemia/reperfusion injury, and the Ca²⁺-Alix-Ist1 axis plays an essential role in recruiting Vps4a to the injured site. Mechanistically, Vps4a promotes the shedding of plasma membrane blebs to restrict permeability to the extracellular environment, and the surveillance of membrane integrity requires the ATPase activity of Vps4a.</p><p><strong>Conclusions: </strong>These results demonstrate that Vps4a-mediated plasma membrane repair is an intrinsic cell protection machinery that antagonizes cardiac ischemia/reperfusion injury, and our findings may contribute to the development of therapeutic strategies towards attenuating cardiac injury.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 3","pages":"279-296"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063994","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":"BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness.","authors":"Yanan Liu, Mengke Li, Zhipeng Chen, Min Zuo, Kaiwen Bao, Ziyan Zhao, Meng Yan, Yongping Bai, Ding Ai, Hu Wang, Hongfeng Jiang","doi":"10.1161/CIRCRESAHA.124.325590","DOIUrl":"10.1161/CIRCRESAHA.124.325590","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)-induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg²⁺/Mn²⁺-dependent 1B)-lysine 63(K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness.</p><p><strong>Methods: </strong>Enzymes governing PPM1B deubiquitination were identified through small interfering RNA (siRNA) screening and mass spectrometry. Glutathione S-transferase pull-down, coimmunoprecipitation, protein purification, and immunofluorescence were used to explore the mechanism underlying PPM1B deubiquitination. Doppler ultrasound was used to evaluate HFHSD-induced arterial stiffness in mice, and telemetry was used to record pulsatile (systolic and diastolic) blood pressure.</p><p><strong>Results: </strong>Smooth muscle cell-specific PPM1B overexpression attenuated HFHSD-induced arterial stiffness in mice in a PPM1B-K326-K63-linked polyubiquitination-dependent manner. Mechanistically, ABRO1 (Abraxas brother 1; a core BRCC36 [BRCA1/BRCA2 (breast cancer type 1/2)-containing complex subunit 36] isopeptidase complex component) directly bound YAP and underwent liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, which in turn promoted PPM1B deubiquitination. Furthermore, smooth muscle cell-specific <i>Abro1</i>-knockout mice and <i>Brcc3</i>-knockout mice showed attenuated HFHSD-induced arterial stiffness and activation of transforming growth factor-β-Smad (mothers against decapentaplegic homolog) signaling.</p><p><strong>Conclusions: </strong>We elucidated the PPM1B deubiquitination mechanisms and highlighted a potential therapeutic target for metabolic syndrome-related arterial stiffness.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"297-314"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913593","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":"Preservation of Vascular Endothelial Function in Late-Onset Postmenopausal Women.","authors":"Sanna Darvish, Kevin O Murray, Katelyn R Ludwig, Krisha H Avalani, Daniel H Craighead, Kaitlin A Freeberg, Shaun Bevers, Julie A Reisz, Angelo D'Alessandro, Kerrie L Moreau, Douglas R Seals, Matthew J Rossman","doi":"10.1161/CIRCRESAHA.124.325639","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325639","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal women (PMW) who complete menopause at a late age (55+ years) have lower cardiovascular disease risk than PMW who complete menopause at a normal age (45-54 years). However, the influence of late-onset menopause on vascular endothelial dysfunction is unknown. Moreover, the mechanisms by which a later age at menopause may modulate endothelial function remain to be determined.</p><p><strong>Methods: </strong>We measured endothelial function (brachial artery flow-mediated dilation [FMD_BA]) in age-matched late- and normal-onset PMW and a young premenopausal reference group. We determined mitochondrial reactive oxygen species (mitoROS)-related suppression of endothelial function (change in FMD_BA with an acute dose of the mitochondria-targeted antioxidant MitoQ; ΔFMD_{BA, MTQ}) in PMW. The effects of serum from late- and normal-onset PMW and premenopausal women on mitoROS bioactivity in human aortic endothelial cells in culture were assessed. Metabolomics analyses in combination with serum metabolite level normalization and human aortic endothelial cell serum exposure experiments were performed to identify the circulating factors contributing to the serum effects on endothelial cell mitoROS bioactivity.</p><p><strong>Results: </strong>FMD_BA in PMW was lower than in premenopausal women. However, FMD_BA was >50% higher in late- versus normal-onset PMW and positively related to age at menopause. ΔFMD_{BA, MTQ} was >50% lower in late- versus normal-onset PMW. Serum from normal-onset PMW but not late-onset PMW induced higher mitoROS bioactivity in human aortic endothelial cells compared with serum from premenopausal women. mitoROS bioactivity was negatively related to FMD_BA and age at menopause. Seventeen metabolites significantly differed between late- and normal-onset PMW; 15 were lipid specific; 8 were triglyceride derived. TG(16:0) was most strongly correlated with mitoROS bioactivity. Normalization of TG(16:0) concentrations in serum from premenopausal women and late-onset PMW to match serum levels in normal-onset PMW abrogated differences in mitoROS bioactivity in serum-treated human aortic endothelial cells.</p><p><strong>Conclusions: </strong>Late-onset menopause is associated with preservation of endothelial function, which is mediated by lower mitoROS-associated oxidative stress. A more favorable profile of circulating lipid metabolites, specifically triglyceride-derived metabolites, contributes to lower endothelial cell mitoROS in late-onset PMW. These findings provide new insight into the possible mechanisms of reduced cardiovascular disease risk in late-onset menopause.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063987","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":"Micro RNA Regulating a Mega Difference in Male and Female Cardiac Physiology.","authors":"Wyatt G Paltzer, James F Martin","doi":"10.1161/CIRCRESAHA.124.325941","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325941","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 3","pages":"276-278"},"PeriodicalIF":16.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063992","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}