Circulation最新文献

{"title":"Extracellular RIPK3 Acts as a Danger-Associated Molecular Pattern to Exaggerate Cardiac Ischemia/Reperfusion Injury.","authors":"Wenjia Zhang,Junxia Zhang,Zeyuan Wang,Ting Li,Liu Changyun,Xuya Kang,Xiaomeng Cui,Jingli Yang,Huilin Qu,Jiaxin Duanmu,Ying Peng,Kai Wang,Li Jin,Peng Xie,Wen Zheng,Haibao Shang,Yahan Liu,Zhuang Tian,Zhenyu Liu,Ye Jin,Yingjia Li,Nan Li,Xiaozhen Zhuo,Yue Wu,Xiaolu Shi,Runhao Ma,Yueshen Sun,Kai Zhang,Xiangming Fang,Xiaomin Hu,Erdan Dong,Shuyang Zhang,Yan Zhang","doi":"10.1161/circulationaha.123.068595","DOIUrl":"https://doi.org/10.1161/circulationaha.123.068595","url":null,"abstract":"BACKGROUNDCardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease. Currently, there is no effective therapy for reducing cardiac I/R injury. Damage-associated molecular patterns are endogenous molecules released after cellular damage to exaggerate tissue inflammation and injury. RIPK3 (receptor-interacting protein kinase 3), a well-established intracellular mediator of cell necroptosis and inflammation, serves as a circulating biomarker of multiple diseases. However, whether extracellular RIPK3 also exerts biological functions in cardiac I/R injury remains totally unknown.METHODSPatients with acute myocardial infarction receiving percutaneous coronary intervention (PCI) were recruited independently in the discovery cohort (103 patients) and validation cohort (334 patients), and major adverse cardiovascular events were recorded. Plasma samples were collected before and after PCI (6 and 24 h) for RIPK3 concentration measurement. Cultured neonatal rat ventricular myocytes, macrophages and endothelial cells, and in vivo mouse models with myocardial injury induced by I/R (or hypoxia/reoxygenation) were used to investigate the role and mechanisms of extracellular RIPK3. Another cohort including patients with acute myocardial infarction receiving PCI and healthy volunteers was recruited to further explore the mechanisms of extracellular RIPK3.RESULTSIn the discovery cohort, elevated plasma RIPK3 levels after PCI are associated with poorer short- and long-term outcomes in patients with acute myocardial infarction, as confirmed in the validation cohort. In both cultured cells and in vivo mouse models, recombinant RIPK3 protein exaggerated myocardial I/R (or hypoxia/reoxygenation) injury, which was alleviated by the RIPK3 antibody. Mechanistically, RIPK3 acted as a damage-associated molecular pattern and bound with RAGE (receptor of advanced glycation end-products), subsequently activating CaMKII (Ca2+/calmodulin-dependent kinase II) to elicit the detrimental effects. The positive correlation between plasma RIPK3 concentrations and CaMKII phosphorylation in human peripheral blood mononuclear cells was confirmed.CONCLUSIONSWe identified the positive relationship between plasma RIPK3 concentrations and the risk of major adverse cardiovascular events in patients with acute myocardial infarction receiving PCI. As a damage-associated molecular pattern, extracellular RIPK3 plays a causal role in multiple pathological conditions during cardiac I/R injury through RAGE/CaMKII signaling. These findings expand our understanding of the physiological and pathological roles of RIPK3, and also provide a promising therapeutic target for myocardial I/R injury and the associated complications.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443744","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":"Social Determinants of Cardiovascular Health in Asian Americans: A Scientific Statement From the American Heart Association.","authors":"Nilay S Shah, Namratha R Kandula, Yvonne Commodore-Mensah, Brittany N Morey, Shivani A Patel, Sally Wong, Eugene Yang, Stella Yi","doi":"10.1161/CIR.0000000000001278","DOIUrl":"10.1161/CIR.0000000000001278","url":null,"abstract":"<p><p>To achieve cardiovascular health (CVH) equity in the United States, an understanding of the social and structural factors that contribute to differences and disparities in health is necessary. The Asian American population is the fastest-growing racial group in the United States but remains persistently underrepresented in health research. There is heterogeneity in how individual Asian American ethnic groups experience CVH and cardiovascular disease outcomes, with certain ethnic groups experiencing a higher burden of adverse social conditions, disproportionately high burden of suboptimal CVH, or excess adverse cardiovascular disease outcomes. In this scientific statement, upstream structural and social determinants that influence CVH in the Asian American population are highlighted, with particular emphasis on the role of social determinants of health across disaggregated Asian American ethnic groups. Key social determinants that operate in Asian American communities include socioeconomic position, immigration and nativity, social and physical environments, food and nutrition access, and health system-level factors. The role of underlying structural factors such as health, social, and economic policies and structural racism is also discussed in the context of CVH in Asian Americans. To improve individual-, community-, and population-level CVH and to reduce CVH disparities in Asian American ethnic subgroups, multilevel interventions that address adverse structural and social determinants are critical to achieve CVH equity for the Asian American population. Critical research gaps for the Asian American population are given, along with recommendations for strategic approaches to investigate social determinants of health and intervene to reduce health disparities in these communities.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281281","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":"Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.","authors":"Long Nguyen-Hoang, Linh Thuy Dinh, Angela S T Tai, Duy-Anh Nguyen, Ritsuko K Pooh, Arihiro Shiozaki, Mingming Zheng, Yali Hu, Bin Li, Aditya Kusuma, Piengbulan Yapan, Arundhati Gosavi, Mayumi Kaneko, Suchaya Luewan, Tung-Yao Chang, Noppadol Chaiyasit, Tongta Nanthakomon, Huishu Liu, Steven W Shaw, Wing Cheong Leung, Zaleha Abdullah Mahdy, Angela Aguilar, Hillary H Y Leung, Nikki M W Lee, So Ling Lau, Isabella Y M Wah, Xiaohong Lu, Daljit S Sahota, Marc K C Chong, Liona C Poon","doi":"10.1161/CIRCULATIONAHA.124.069907","DOIUrl":"10.1161/CIRCULATIONAHA.124.069907","url":null,"abstract":"<p><strong>Background: </strong>This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia.</p><p><strong>Methods: </strong>Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular 6-week intervals, one cluster was randomized to transit from nonintervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm preeclampsia using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm preeclampsia ≥1 in 100, received low-dose aspirin from <16 weeks until 36 weeks.</p><p><strong>Results: </strong>Overall, 88.04% (42 897 of 48 725) of women agreed to undergo first-trimester screening for preterm preeclampsia. Among those identified as high-risk in the intervention phase, 82.39% (2919 of 3543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm preeclampsia between the intervention and non-intervention phases (adjusted odds ratio [aOR], 1.59 [95% CI, 0.91-2.77]). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm preeclampsia (aOR, 0.59 [95% CI, 0.37-0.92]). In addition, it correlated with 54%, 55%, and 64% reduction in the incidence of preeclampsia with delivery at <34 weeks (aOR, 0.46 [95% CI, 0.23-0.93]), spontaneous preterm birth <34 weeks (aOR, 0.45 [95% CI, 0.22-0.92]), and perinatal death (aOR, 0.34 [95% CI, 0.12-0.91]), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events.</p><p><strong>Conclusions: </strong>The implementation of the screen-and-prevent strategy for preterm preeclampsia is not associated with a significant reduction in the incidence of preterm preeclampsia. However, low-dose aspirin effectively reduces the incidence of preterm preeclampsia by 41% among high-risk women. The screen-and-prevent strategy for preterm preeclampsia is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm preeclampsia on a global scale.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03941886.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455692","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":"Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response.","authors":"Christoph Hofmann, Adrian Serafin, Ole M Schwerdt, Johannes Fischer, Florian Sicklinger, Fereshteh S Younesi, Nikole J Byrne, Ingmar S Meyer, Ellen Malovrh, Clara Sandmann, Lonny Jürgensen, Verena Kamuf-Schenk, Claudia Stroh, Zoe Löwenthal, Daniel Finke, Etienne Boileau, Arica Beisaw, Heiko Bugger, Mandy Rettel, Frank Stein, Hugo A Katus, Tobias Jakobi, Norbert Frey, Florian Leuschner, Mirko Völkers","doi":"10.1161/CIRCULATIONAHA.123.067479","DOIUrl":"10.1161/CIRCULATIONAHA.123.067479","url":null,"abstract":"<p><strong>Background: </strong>The myocardium adapts to ischemia/reperfusion (I/R) by changes in gene expression, determining the cardiac response to reperfusion. mRNA translation is a key component of gene expression. It is largely unknown how regulation of mRNA translation contributes to cardiac gene expression and inflammation in response to reperfusion and whether it can be targeted to mitigate I/R injury.</p><p><strong>Methods: </strong>To examine translation and its impact on gene expression in response to I/R, we measured protein synthesis after reperfusion in vitro and in vivo. Underlying mechanisms of translational control were examined by pharmacological and genetic targeting of translation initiation in mice. Cell type-specific ribosome profiling was performed in mice that had been subjected to I/R to determine the impact of mRNA translation on the regulation of gene expression in cardiomyocytes. Translational regulation of inflammation was studied by quantification of immune cell infiltration, inflammatory gene expression, and cardiac function after short-term inhibition of translation initiation.</p><p><strong>Results: </strong>Reperfusion induced a rapid recovery of translational activity that exceeds baseline levels in the infarct and border zone and is mediated by translation initiation through the mTORC1 (mechanistic target of rapamycin complex 1)-4EBP1 (eIF4E-binding protein 1)-eIF (eukaryotic initiation factor) 4F axis. Cardiomyocyte-specific ribosome profiling identified that I/R increased translation of mRNA networks associated with cardiac inflammation and cell infiltration. Short-term inhibition of the mTORC1-4EBP1-eIF4F axis decreased the expression of proinflammatory cytokines such as Ccl2 (C-C motif chemokine ligand 2) of border zone cardiomyocytes, thereby attenuating Ly6C^hi monocyte infiltration and myocardial inflammation. In addition, we identified a systemic immunosuppressive effect of eIF4F translation inhibitors on circulating monocytes, directly inhibiting monocyte infiltration. Short-term pharmacological inhibition of eIF4F complex formation by 4EGI-1 or rapamycin attenuated translation, reduced infarct size, and improved cardiac function after myocardial infarction.</p><p><strong>Conclusions: </strong>Global protein synthesis is inhibited during ischemia and shortly after reperfusion, followed by a recovery of protein synthesis that exceeds baseline levels in the border and infarct zones. Activation of mRNA translation after reperfusion is driven by mTORC1/eIF4F-mediated regulation of initiation and mediates an mRNA network that controls inflammation and monocyte infiltration to the myocardium. Transient inhibition of the mTORC1-/eIF4F axis inhibits translation and attenuates Ly6C^hi monocyte infiltration by inhibiting a proinflammatory response at the site of injury and of circulating monocytes.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104930","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":"Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension.","authors":"Jason Hong, Lejla Medzikovic, Wasila Sun, Brenda Wong, Grégoire Ruffenach, Christopher J Rhodes, Adam Brownstein, Lloyd L Liang, Laila Aryan, Min Li, Arjun Vadgama, Zeyneb Kurt, Tae-Hwi Schwantes-An, Elizabeth A Mickler, Stefan Gräf, Mélanie Eyries, Katie A Lutz, Michael W Pauciulo, Richard C Trembath, Frédéric Perros, David Montani, Nicholas W Morrell, Florent Soubrier, Martin R Wilkins, William C Nichols, Micheala A Aldred, Ankit A Desai, David-Alexandre Trégouët, Soban Umar, Rajan Saggar, Richard Channick, Rubin M Tuder, Mark W Geraci, Robert S Stearman, Xia Yang, Mansoureh Eghbali","doi":"10.1161/CIRCULATIONAHA.124.069864","DOIUrl":"10.1161/CIRCULATIONAHA.124.069864","url":null,"abstract":"<p><strong>Background: </strong>Integrative multiomics can elucidate pulmonary arterial hypertension (PAH) pathobiology, but procuring human PAH lung samples is rare.</p><p><strong>Methods: </strong>We leveraged transcriptomic profiling and deep phenotyping of the largest multicenter PAH lung biobank to date (96 disease and 52 control) by integration with clinicopathologic data, genome-wide association studies, Bayesian regulatory networks, single-cell transcriptomics, and pharmacotranscriptomics.</p><p><strong>Results: </strong>We identified 2 potentially protective gene network modules associated with vascular cells, and we validated <i>ASPN</i>, coding for asporin, as a key hub gene that is upregulated as a compensatory response to counteract PAH. We found that asporin is upregulated in lungs and plasma of multiple independent PAH cohorts and correlates with reduced PAH severity. We show that asporin inhibits proliferation and transforming growth factor-β/phosphorylated SMAD2/3 signaling in pulmonary artery smooth muscle cells from PAH lungs. We demonstrate in Sugen-hypoxia rats that <i>ASPN</i> knockdown exacerbated PAH and recombinant asporin attenuated PAH.</p><p><strong>Conclusions: </strong>Our integrative systems biology approach to dissect the PAH lung transcriptome uncovered asporin as a novel protective target with therapeutic potential in PAH.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":35.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016568","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":"Optical Spectroscopic Detection and Typing of Cardiac Amyloidosis.","authors":"Sudipta S Mukherjee,Joseph J Maleszewski,Daniel Luthringer,Matthew P Confer,Anirudh Mittal,Surendra Dasari,Ellen D McPhail,Suraj Kapa,Thenkurussi Kesavadas,Andre Kajdacsy-Balla,Evan Kransdorf,Jai Raman,Rohit Bhargava","doi":"10.1161/circulationaha.124.069554","DOIUrl":"https://doi.org/10.1161/circulationaha.124.069554","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439291","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":"Patients With Advanced Heart Failure and Atrial Fibrillation Deserve an Attempt at Catheter Ablation as First-Line Therapy.","authors":"Christian Sohns,Philipp Sommer","doi":"10.1161/circulationaha.124.069759","DOIUrl":"https://doi.org/10.1161/circulationaha.124.069759","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439426","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":"Response by Hoedemakers et al to Letter Regarding Article, \"mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis\".","authors":"Sarah Hoedemakers,Bernard Cosyns,Steven Droogmans,Frederik H Verbrugge,Lieven Herbots,Jan Verwerft","doi":"10.1161/circulationaha.124.071022","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071022","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439427","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":"Pathogenesis of Atherothrombotic Events: From Lumen to Lesion and Beyond.","authors":"Peter Libby","doi":"10.1161/circulationaha.124.070087","DOIUrl":"https://doi.org/10.1161/circulationaha.124.070087","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439493","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":"Letter by Jha Regarding Article, \"mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis\".","authors":"Ajay Kumar Jha","doi":"10.1161/circulationaha.124.070147","DOIUrl":"https://doi.org/10.1161/circulationaha.124.070147","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":null,"pages":null},"PeriodicalIF":37.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439288","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}