Circulation最新文献

{"title":"Nrf3-Mediated Mitochondrial Superoxide Promotes Cardiomyocyte Apoptosis and Impairs Cardiac Functions by Suppressing Pitx2.","authors":"Qishan Chen, Ancheng Zheng, Xiaolei Xu, Zhenning Shi, Mei Yang, Shasha Sun, Leyu Wang, Yumeng Wang, Haige Zhao, Qingzhong Xiao, Li Zhang","doi":"10.1161/CIRCULATIONAHA.124.070286","DOIUrl":"10.1161/CIRCULATIONAHA.124.070286","url":null,"abstract":"<p><strong>Background: </strong>Myocardial infarction (MI) elicits mitochondria reactive oxygen species (ROS) production and cardiomyocyte (CM) apoptosis. Nrf3 (nuclear factor erythroid 2-related factor 3) has an established role in regulating redox signaling and tissue homeostasis. Here, we aimed to evaluate the role and mechanism of Nrf3 in injury-induced pathological cardiac remodeling.</p><p><strong>Methods: </strong>Global (Nrf3-KO) and CM-specific (Nrf3<sup>△CM</sup>) Nrf3 knockout mice were subjected to MI or ischemia/reperfusion injury, followed by functional and histopathological analysis. Primary neonatal mouse and rat ventricular myocytes and CMs derived from human induced pluripotent stem cells were used to evaluate the impact of Nrf3 on CM apoptosis and mitochondrial ROS production. Chromatin immunoprecipitation sequencing and immunoprecipitation-mass spectrometry analysis were used to uncover potential targets of Nrf3. MitoParaquat administration and CM-specific adeno-associated virus vectors were used to further confirm the <i>i</i>n vivo relevance of the identified signal pathways.</p><p><strong>Results: </strong>Nrf3 was expressed mainly in CMs in healthy human hearts, and an increased level of Nrf3 was observed in CMs within the border zone of infarcted human hearts and murine cardiac tissues after MI. Both global and CM-specific Nrf3 knockout significantly decreased injury-induced mitochondrial ROS production, CM apoptosis, and pathological cardiac remodeling, consequently improving cardiac functions. In addition, cardiac-specific Nrf3 overexpression reversed the ameliorative cardiac phenotypes observed in Nrf3-KO mice. Functional studies showed that Nrf3 promoted neonatal mouse ventricular myocyte, neonatal rat ventricular myocyte, and CMs derived from human induced pluripotent stem cell apoptosis by increasing mitochondrial ROS production. Critically, augmenting mitochondrial ROS with MitoParaquat blunted the beneficial effects of Nrf3 deletion on cardiac function and remodeling. Mechanistically, a redox regulator Pitx2 (paired-like homeodomain transcription factor 2) was identified as one of the main target genes of Nrf3. Specifically, Nrf3 binds to <i>Pitx2</i> promoter, where it increases DNA methylation through recruiting heterogeneous nuclear ribonucleoprotein K and DNA-methyltransferase 1 complex, thereby inhibiting Pitx2 expression. CM-specific knockdown of Pitx2 blunted the beneficial effects of Nrf3 deletion on cardiac function and remodeling, and cardiac-specific Pitx2 overexpression attenuated MI-induced mitochondrial ROS production and CM apoptosis, as well as preserved cardiac functions after MI.</p><p><strong>Conclusions: </strong>Nrf3 promotes injury-induced CM apoptosis and deteriorates cardiac functions by increasing mitochondrial ROS production through suppressing Pitx2 expression. Targeting the Nrf3-Pitx2-mitochondrial ROS signal axis may therefore represent a novel therapeutic approach for MI treatment.</p","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1024-1046"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647524","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":"Correction to: Principles for the Future of Biomedical Research in the United States and Optimizing the National Institutes of Health: A Presidential Advisory From the American Heart Association.","authors":"Joseph C Wu, Donna K Arnett, Ivor J Benjamin, Mark A Creager, Robert A Harrington, Joseph A Hill, P Michael Ho, Steven R Houser, Stephanie Scarmo, Svati H Shah, Gordon F Tomaselli","doi":"10.1161/CIR.0000000000001327","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001327","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 14","pages":"e919"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802753","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":"Correction to: 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/CIR.0000000000001331","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001331","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 14","pages":"e921"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802708","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":"Principles for the Future of Biomedical Research in the United States and Optimizing the National Institutes of Health: A Presidential Advisory From the American Heart Association.","authors":"Joseph C Wu, Donna K Arnett, Ivor J Benjamin, Mark A Creager, Robert A Harrington, Joseph A Hill, P Michael Ho, Steven R Houser, Stephanie Scarmo, Svati H Shah, Gordon F Tomaselli","doi":"10.1161/CIR.0000000000001319","DOIUrl":"10.1161/CIR.0000000000001319","url":null,"abstract":"<p><p>Groundbreaking achievements in science and medicine have contributed to reductions in cardiovascular disease and stroke mortality over the past 7 decades. Many of these advances were supported through investments by the National Institutes of Health, the global leader in funding biomedical research. This public investment has produced important economic returns, including supporting >400 000 jobs and roughly $93 billion in economic activity in the United States. Unfortunately, public funding has not kept pace with the burden of disease or rates of inflation. As the nation's oldest and largest volunteer organization dedicated to fighting heart disease and stroke, research is critical to the American Heart Association's mission. Given the American Heart Association's unique position in representation of patients, clinicians, and scientists and as a research funder, we offer the following principles to optimize the future of the US biomedical research enterprise in general and the National Institutes of Health in particular. Specifically, the United States should continue to prioritize innovative and impactful research; to improve efficiency and transparency in its peer review process; to lead in translating evidence into practice; to support the current and future biomedical workforce; and to ensure robust and reliable public investment for the future. The American Heart Association reiterates our strong support for the National Institutes of Health and federal agencies that fund and implement biomedical and population-based research initiatives, which yield important economic returns. These agencies are vital to support today's current and future health challenges, to drive foundational science, to improve patient health, to reduce the global disease burden, to address upstream and preventive strategies, and to improve the value of our public health and health care investments.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e867-e876"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448203","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":"Correction to: Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration-Tobacco Working Group.","authors":"Zhiqi Yao, Erfan Tasdighi, Zeina A Dardari, Kunal K Jha, Ngozi Osuji, Tanuja Rajan, Ellen Boakye, Carlos J Rodriguez, Kunihiro Matsushita, Eleanor M Simonsick, Joao A C Lima, Rachel Widome, Debbie L Cohen, Lawrence J Appel, Amit Khera, Michael E Hall, Suzanne Judd, Shelley A Cole, Ramachandran S Vasan, Emelia J Benjamin, Aruni Bhatnagar, Andrew P DeFilippis, Michael J Blaha","doi":"10.1161/CIR.0000000000001322","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001322","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 14","pages":"e922"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802690","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":"Predicting Cardiovascular Risk With Use of Various Tobacco Products.","authors":"Neal L Benowitz","doi":"10.1161/CIRCULATIONAHA.125.073894","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.073894","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 14","pages":"1006-1008"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802756","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":"Relation of Low-Density Lipoprotein Cholesterol, High-Sensitivity C-Reactive Protein, and Lipoprotein(a) Each to Future Cardiovascular Events and Death After Acute Coronary Syndrome on High-Intensity Statin Therapy: An Analysis of the Placebo Arm of ODYSSEY OUTCOMES.","authors":"P Gabriel Steg, Michael Szarek, J Wouter Jukema, Deepak L Bhatt, Vera A Bittner, Rafael Diaz, Sergio Fazio, Geneviève Garon, Shaun G Goodman, Robert A Harrington, Harvey D White, Andreas M Zeiher, Gregory G Schwartz","doi":"10.1161/CIRCULATIONAHA.124.071269","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071269","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 14","pages":"1047-1050"},"PeriodicalIF":35.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802757","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":"Role of Technology in Promoting Heart Healthy Behavior Change to Increase Equity in Optimal Cardiovascular Health: A Scientific Statement From the American Heart Association.","authors":"Tiffany M Powell-Wiley, LaPrincess C Brewer, Lora E Burke, Rosalba Hernandez, Jill Landsbaugh Kaar, Maura Kepper, Christopher E Kline, Keila N Lopez, Shamarial Roberson, Colleen K Spees, Gerald J Jerome","doi":"10.1161/CIR.0000000000001314","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001314","url":null,"abstract":"<p><p>Populations most affected by cardiovascular health disparities, including underrepresented populations with lower socioeconomic status, people with disabilities, and those living in underserved rural communities, are disproportionately exposed to adverse social determinants of health. Specifically, economic instability and suboptimal living conditions within the neighborhood and built environment directly determine access to resources and opportunities for healthful behaviors. In this scientific statement, we examined the technology-enabled interventions that address cardiovascular health behaviors from adolescence to adulthood in populations most affected by health disparities. We used a broad definition of technology, including wearables, applications, and telehealth, for behavior tracking. Aligning with Life's Essential 8, we focused on interventions targeting behavior change related to physical activity, sedentary time, dietary intake, tobacco cessation, and sleep health to improve cardiovascular health. The digital determinants of health are important adjuncts to the social determinants and operate at the individual, interpersonal, community, and societal levels. The digital determinants of health include the impact of digital technologies (eg, wearables, telemedicine) across health outcomes. Evidence of effective interventions using technology to improve cardiovascular health through positive behavior change is critical for preventing cardiovascular disease events. Stronger evidence is needed to inform and implement effective approaches that are scalable and cost-effective across communities and health care institutions to advance digital equity in cardiovascular health. Dissemination of digital solutions to improve cardiovascular health in communities or across health care systems must ensure effective, feasible, available, and affordable solutions for populations most in need.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794863","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":"Racial Disparities in Long-Term Outcomes After Endovascular Aortic Aneurysm Repair in Black and White Medicare Beneficiaries.","authors":"Abena Appah-Sampong, Christina Marcaccio, Siling Li, Yang Song, Mohamad A Hussain, Robert Yeh, Marc L Schermerhorn, Eric A Secemsky","doi":"10.1161/CIRCULATIONAHA.124.072018","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072018","url":null,"abstract":"<p><strong>Background: </strong>Despite reported racial disparities between Black and White adults in short-term outcomes after abdominal aortic aneurysmal intervention, there is a paucity of literature aimed at understanding long-term disparities. The present study aims to characterize racial disparities in long-term outcomes, perioperative outcomes, and health care use after endovascular aortic aneurysm repair.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study from 2011 to 2019 with outcome assessment through 2020. Using a 100% sample of national Medicare data, we identified beneficiaries ≥66 years of age who underwent intact infrarenal endovascular aortic aneurysm repair. The primary outcome was a composite of endovascular or open aortic reintervention, late aneurysm rupture, and all-cause mortality. Secondary outcomes included other reinterventions, perioperative outcomes, and annual rates of health care use.</p><p><strong>Results: </strong>A cohort of 107 636 Black (3.9%) and White (96.1%) beneficiaries was identified. The cumulative incidence of the primary outcome was 72.9% (95% CI, 71.8%-73.9%) in White patients versus 80.0% (95% CI, 76.4-83.0) in Black patients (<i>P</i><0.0001). The adjusted hazard of the primary outcome was not significantly different between Black and White adults (adjusted hazard ratio [HR] 1.04 [95% CI, 0.99-1.09]); however, when death was treated as a competing risk, a significantly higher hazard for the composite outcome was observed for Black patients (subdistribution HR, 1.56 [95% CI, 1.39-1.76]). Components of the primary outcome were also greater among Black compared with White patients. Black patients had higher rates of medical complications in the perioperative period, including acute renal failure (subdistribution HR, 1.18 [95% CI, 1.01-1.38]), dialysis initiation (subdistribution HR, 2.75 [95% CI, 2.03-3.7]), and deep vein thrombosis (subdistribution HR, 1.54 [95% CI, 1.05-2.26]). Black patients had lower rates of vascular office visits after intervention (adjusted rate ratio, 0.96 [95% CI, 0.93-0.99]) but higher rates of emergency department visits (adjusted rate ratio, 1.05 [95% CI, 1.02-1.09]) and hospital readmissions (adjusted rate ratio, 1.13 [95% CI, 1.08-1.18]).</p><p><strong>Conclusions: </strong>Black patients demonstrated increased risk of late aortic-related events after endovascular aortic aneurysm repair after accounting for the competing risk of death and controlling for baseline covariates. Further investigation into preoperative medical management and barriers to postoperative health care access is necessary to further elucidate underlying mechanisms for the observed disparities.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794859","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":"Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes.","authors":"Arisa Sittichokkananon, Victoria Garfield, Scott T Chiesa","doi":"10.1161/CIRCULATIONAHA.124.070632","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.070632","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) and dementia. We examined whether an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer's, or vascular dementia, and investigated whether differences in potentially modifiable lifestyle factors in the mid- to late-life period may attenuate this risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A prospective cohort study of 365 782 participants free from dementia for at least 5 years after baseline assessment was conducted within the UK Biobank cohort. Genetic risk was assessed using a genomewide polygenic risk score (PRS) for CAD and lifestyle risk using a modified version of the American Heart Association's Life's Essential 8 Lifestyle Risk Score (LRS). Higher values for both scores were deemed to represent increased risk. Primary outcomes were incident all-cause, Alzheimer's, and vascular dementia diagnoses obtained from electronic health records. Secondary outcomes were neuroimaging phenotypes measured in 32 028 participants recalled for magnetic resonance imaging. Sensitivity analyses were conducted to test the extent by which biological and behavioral risk factors contributed to observed associations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 8870 cases of all-cause dementia were observed over a median 13.9-year follow-up. Both genetic (PRS) and lifestyle (LRS) risk scores for CAD were associated with a modestly elevated risk of all-cause dementia (subhazard ratio per SD increase, 1.10 [1.08, 1.12], &lt;i&gt;P&lt;/i&gt;&lt;0.001, for PRS and 1.04 [1.02, 1.06], &lt;i&gt;P&lt;/i&gt;=0.006, for LRS). This risk appeared largely attributable to underlying vascular dementia diagnoses (subhazard ratio, 1.16 [1.11, 1.21], &lt;i&gt;P&lt;/i&gt;&lt;0.001 for PRS and 1.15 [1.09, 1.22], &lt;i&gt;P&lt;/i&gt;&lt;0.001, for LRS), because Alzheimer's disease was found to demonstrate moderate associations with PRS alone (subhazard ratio, 1.09 [1.06, 1.13]; &lt;i&gt;P&lt;/i&gt;&lt;0.001). LRS was found to have an additive rather than interactive effect with PRS, with individuals in the highest tertiles for both genetic and lifestyle risk for CAD ≈70% more likely to develop vascular dementia during follow-up compared with those in the lowest tertiles for both (subhazard ratio, 1.71 [1.39, 2.11]; &lt;i&gt;P&lt;/i&gt;&lt;0.001). This was substantially attenuated in those with a low LRS at baseline, however, regardless of underlying genetic risk (40% to 50% reduction for low versus high LRS tertile regardless of PRS tertile; &lt;i&gt;P&lt;/i&gt;&lt;0.001 for all). In a subset of individuals recalled for neuroimaging assessments, those in the highest tertiles for genetic and lifestyle risk for CAD demonstrated a ≈25% greater volume of white matter hyperintensities than those in the lowest risk tertiles, but showed little difference in gray matter or hippocampal volumes. Sensitivity analyses identified associations between both biological and behavioral risk scores with white matter hyperin","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779268","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}