Circulation research最新文献

{"title":"Overexpression of Wild-Type TMEM43 Improves Cardiac Function in Arrhythmogenic Right Ventricular Cardiomyopathy Type 5.","authors":"Laura Lalaguna, María Arévalo-Núñez de Arenas, Marina López-Olañeta, María Villalba-Orero, Rafael J Jiménez-Riobóo, María Victoria Gómez-Gaviro, Joan Isern, Pura Muñoz-Cánoves, Barry J Byrne, Juan Pablo Ochoa, Pablo García-Pavía, Enrique Lara-Pezzi","doi":"10.1161/CIRCRESAHA.124.325848","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325848","url":null,"abstract":"<p><strong>Background: </strong>Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) is the most aggressive type of ARVC, caused by a fully penetrant missense mutation (p.S358L) in TMEM43 (transmembrane protein 43). Pathologically, the disease is characterized by dilation of the cardiac chambers and fibrofatty replacement of the myocardium, which results in heart failure and sudden cardiac death. Current therapeutic options are limited, and no specific therapies targeting the primary cause of the disease have been proposed.</p><p><strong>Methods: </strong>We investigated whether overexpression of wild-type (WT) TMEM43 could overcome the detrimental effects of the mutant form. We used transgenic mouse models overexpressing either WT or mutant (S358L) TMEM43 to generate a double transgenic mouse line overexpressing both forms of the protein. In addition, we explored if systemic delivery of a codon-optimized self-complementary adeno-associated virus bearing WT-TMEM43 could improve disease progression assessed by ECG and echocardiography.</p><p><strong>Results: </strong>Double transgenic mice overexpressing both WT and mutant TMEM43 forms showed delayed ARVC5 onset, improved cardiac contraction, and reduced ECG abnormalities compared with mice expressing S358L-TMEM43. In addition, cardiomyocyte death and myocardial fibrosis were reduced, with an overall increase in survival. Finally, we demonstrated that a single systemic administration of an adeno-associated virus carrying codon-optimized WT-TMEM43 prevents ventricular dysfunction and ECG abnormalities induced by S358L-TMEM43.</p><p><strong>Conclusions: </strong>Overexpression of WT-TMEM43 improves the pathological phenotype in a mouse model of ARVC5. Adeno-associated virus-mediated delivery of WT-TMEM43 offers a promising and specific therapy for patients suffering from this highly lethal disease.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05885412, NCT06109181, and NCT06228924.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":16.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647299","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":"Advances in Our Understanding of Cardiovascular Diseases After Preeclampsia.","authors":"Malamo E Countouris, Natalie A Bello","doi":"10.1161/CIRCRESAHA.124.325581","DOIUrl":"10.1161/CIRCRESAHA.124.325581","url":null,"abstract":"<p><p>Preeclampsia is a syndrome of hypertension in association with target organ dysfunction, including proteinuria, which manifests during pregnancy and the immediate postpartum period. The pathophysiology of preeclampsia originates from impaired trophoblastic invasion of the placental resulting in malperfusion and involves multiple mechanistic pathways that include anti-angiogenic factors, endothelial dysfunction, and immune dysregulation. Preeclampsia caries an increased risk of subclinical cardiovascular disease including left ventricular remodeling, diastolic dysfunction, coronary artery calcification, peripheral vascular abnormalities, and microvascular dysfunction and clinical cardiovascular disease including stroke, heart failure, myocardial infarction, and death from a cardiovascular cause. This review will highlight several common mechanistic pathways shared between preeclampsia and cardiovascular diseases that provide insight into potential targets for risk reduction and disease process mitigation that can be examined in future trials.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"583-593"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623578","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":"Strategies for Overcoming Barriers in Access to Cardiovascular Care for Women.","authors":"Deirdre J Mattina, Michael C Honigberg, Zainab Mahmoud, Karen E Joynt Maddox","doi":"10.1161/CIRCRESAHA.124.325544","DOIUrl":"10.1161/CIRCRESAHA.124.325544","url":null,"abstract":"<p><p>Women face unique barriers to equitable health care. To ensure access to quality cardiovascular care across the lifespan of women, several systemic and social challenges need to be addressed. With the understanding that women often direct health care decisions, not only for themselves but for their family unit as well, a holistic approach to address health care barriers is warranted. This review aims to highlight key barriers to equitable health care access for women and propose potential strategies to overcome these barriers. This review is structured around 5 key areas in which there are gender- or sex-specific barriers to optimal outcomes: (1) insurance-related barriers, (2) geographic and social barriers, (3) health care delivery capacity and workforce issues, (4) quality and accountability measures, and (5) global health challenges. More research is needed on the sustainability, costs, and sex- and gender-specific outcomes of these solutions to drive transformative change.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"628-641"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623676","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":"Introduction to the Compendium on Lifelong Care in Women: Applying a Sex- and Gender-Lens to Practice.","authors":"Kathryn J Lindley","doi":"10.1161/CIRCRESAHA.125.326335","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.125.326335","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"551-552"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623596","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":"Sex-Specific Factors Influencing Obesity in Women: Bridging the Gap Between Science and Clinical Practice.","authors":"Hazem Ayesh, Samar A Nasser, Keith C Ferdinand, Barbara Gisella Carranza Leon","doi":"10.1161/CIRCRESAHA.124.325535","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325535","url":null,"abstract":"<p><p>Obesity in women is a significant public health issue with serious implications for cardiovascular-kidney-metabolic syndrome and cardiovascular disease. This complex challenge is influenced by physiological, hormonal, socioeconomic, and cultural factors. Women face unique weight management challenges due to hormonal changes during pregnancy, perimenopause, and menopause, which affect fat distribution and increase cardiovascular-kidney-metabolic syndrome risk. Current clinical guidelines often overlook these sex-specific factors, potentially limiting the effectiveness of obesity management strategies in women. This review explores the sex-specific aspects of obesity's pathophysiology, epidemiological trends, and associated comorbidities, focusing on cardiovascular and metabolic complications. This review synthesizes literature on obesity in women, emphasizing sex-specific factors influencing its development and progression. It examines the limitations of body mass index as an obesity measure and explores alternative classification methods. Additionally it investigates the relationship between obesity and comorbidities such as diabetes, hypertension, and dyslipidemia, with a focus on postmenopausal women. Obesity in women is linked to increased risks of cardiovascular-kidney-metabolic syndrome and cardiovascular disease. Hormonal fluctuations throughout life contribute to weight gain and fat distribution patterns specific to women, increasing cardiovascular disease risk. Effective obesity management strategies in women must account for these sex-specific variations. Postmenopausal women are particularly affected by obesity-related complications. Lifestyle interventions, pharmacotherapy, and bariatric surgery have shown efficacy in weight management, though success rates vary. Addressing obesity in women requires a comprehensive approach that considers sex-specific physiological factors, life-stage challenges, and sociocultural barriers. Integrating precision medicine and emerging therapies offers potential for more personalized and effective interventions. Personalized strategies that consider women's biological and life-stage challenges can enhance obesity management and improve cardiovascular outcomes. Future research and clinical practice should focus on developing tailored strategies that address women's unique vulnerabilities to obesity and its associated health risks and on validating sex-specific interventions to improve obesity management in women.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"594-605"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623675","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":"Understanding Thoracic Aortic Disease in Women.","authors":"Bana Samman, Mimi X Deng, Jennifer C Y Chung, Maral Ouzounian","doi":"10.1161/CIRCRESAHA.124.325681","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325681","url":null,"abstract":"<p><p>Multifaceted disparities exist between men and women with thoracic aortic aneurysm and dissection. Despite a higher prevalence of thoracic aortic aneurysm and dissection among men, women experience disproportionately accelerated aneurysmal expansion, greater risks of rupture or dissection, and acute aortic syndromes that occur at relatively smaller diameters. In the context of acute type A aortic dissection, they also experience more complications, increased out-of-hospital mortality, delays in presentation and diagnosis, and worse postoperative survival. These gaps are largely driven by sex differences in vascular aging and remodeling, which include arterial stiffening associated with the hormonal changes that occur during menopause. Furthermore, the increased risk of acute type A aortic dissection during pregnancy in women with thoracic aortic disease necessitates a multidisciplinary approach to peripartum counseling and surveillance. Despite significant recent improvements in early postoperative outcomes, other disparities persist, emphasizing the need for sex-specific research, patient counseling, routine monitoring, and surgical thresholds to bridge the gap in outcomes of thoracic aortic care between sexes. Elucidating the underlying mechanisms of aortic aging and its difference between men and women, as well as moving toward personalized management protocols, will give rise to improved outcomes in the treatment of thoracic aortopathy.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"606-617"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623678","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":"Lifelong Care of Females With Congenital Heart Disease.","authors":"Rose Tompkins, Prashanth Venkatesh, Adam J Small, Dan G Halpern","doi":"10.1161/CIRCRESAHA.124.325596","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325596","url":null,"abstract":"<p><p>Medical and surgical advancements of the past 70 years have resulted in a remarkable shift in the natural history of congenital heart disease (CHD) such that survival to adulthood is expected for >90% of children born with congenital heart defects, including those with complex CHD. There are now more adults than children living with CHD, a majority of them are female. As significant strides have been made in the management of adult patients with CHD, there has been an evolving understanding of the important role inherent sex-specific differences play in impacting long-term outcomes for females with CHD including differences in sexual and reproductive health, risk and incidence of acquired cardiovascular disease, and health surveillance. Notably, care for the female CHD patient is a continuum that is not isolated to discrete stages but cumulative of health exposures and experiences over a lifetime. This review aims to provide a brief overview of the current understanding of the unique health needs and considerations for females with CHD over their lifetime for both the pediatric and adult provider to help identify opportunities for care optimization, continue to raise awareness of the necessity of lifelong care and advocate for the critical need of research that prospectively evaluates pregnancy and other health-related exposures on long-term quality of life and survival for females with CHD.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"553-565"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623674","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":"Influence of Primary Neurologic Disease on Cardiovascular Health in Females.","authors":"Khadija Awais Ali, Deborah L G Kerrigan, Jillian Molli Berkman","doi":"10.1161/CIRCRESAHA.124.325545","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325545","url":null,"abstract":"<p><p>Neurocardiology is an interdisciplinary field that examines the complex interactions between the nervous and the cardiovascular systems, exploring how neurological processes, such as autonomic nervous system regulation and brain-heart communication impact heart function and contribute to cardiovascular health and disease. Although much of the focus on cardiovascular health has centered on traditional risk factors, the influence of the nervous system, especially in females, is increasingly recognized as a key determinant of cardiovascular outcomes. This article reviews existing literature on the neurological mechanisms that impact cardiovascular function in females. Specifically, we analyze how primary neurological disorders including cerebrovascular disease, headache disorders, and multiple sclerosis have specific downstream effects on cardiac function. By understanding the complex relationship between neurological and cardiovascular health, this review highlights the need for sex-specific approaches to prevention, diagnosis, and treatment of cardiovascular disease in females, ultimately encouraging the discovery of more effective care strategies and improving health outcomes.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"618-627"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623582","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":"The 2024 US Medical Eligibility Criteria for Contraceptive Use: Application to Practice in the Care of Patients With Cardiac Disease.","authors":"Kayle Shapero, Tessa Madden","doi":"10.1161/CIRCRESAHA.125.325682","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.125.325682","url":null,"abstract":"<p><p>Cardiovascular disease is the leading cause of maternal mortality in the United States, with the majority of deaths stemming from preventable causes. Contraception is one of the tools that can be utilized to prevent mortality and morbidity associated with unplanned pregnancy in patients with underlying congenital or acquired heart disease. There are a wide range of contraceptive methods available. While some methods, especially those containing estrogen, may be associated with increased risks in certain cardiac disease states, intrauterine devices, implants, and progestin-only methods may be safely used by the vast majority of patients with cardiac disease. Furthermore, intrauterine devices and implants are the most effective reversible contraceptive methods available. This review provides a summary of the US Centers for Disease Control and Prevention 2024 Medical Eligibility Criteria for Contraceptive Use as it applies to cardiac disease states. This review emphasizes the importance of contraceptive counseling and aims to familiarize the reader with the various forms of contraception available to patients, as well as the risks and benefits of each method in patients with different types of cardiac disease.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"136 6","pages":"566-582"},"PeriodicalIF":16.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623677","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":"March2 Alleviates Aortic Aneurysm/Dissection by Regulating PKM2 Polymerization.","authors":"Yiran E Li, Shuolin Liu, Litao Wang, Yuxin Du, Lin Wu, Haoran Chen, Tingfang Zhu, Jie Lin, Shengjun Xiong, Yayu Wang, Qijun Zheng, Rongjun Zou, Ling Lin, Zheyun Li, Lixin Wang, Junbo Ge, Jun Ren, Yingmei Zhang","doi":"10.1161/CIRCRESAHA.124.325049","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.124.325049","url":null,"abstract":"<p><strong>Background: </strong>Aortic aneurysm/dissection (AAD) is a life-threatening disease lacking effective pharmacological treatment. Protein ubiquitination plays a pivotal role in cardiovascular diseases. However, the possible contribution of the E3 ubiquitin ligase March2 (membrane-associated RING finger protein 2) to the cause of AAD remains elusive.</p><p><strong>Methods: </strong>Integrated single-cell RNA sequencing analysis was conducted in human AAD tissues. Based on the screening results, we generated a mouse line of smooth muscle cell-specific March2 knockout. β-Aminopropionitrile monofumarate was used to establish AAD. Cleavage under targets and tagmentation and cleavage under targets and tagmentation-quantitative polymerase chain reaction were performed to identify possible target genes for histone H3K18 lactylation.</p><p><strong>Results: </strong>March2 expression was downregulated in aorta from patients with AAD or β-aminopropionitrile monofumarate-induced AAD mice. β-Aminopropionitrile monofumarate-induced AAD was significantly accentuated in March2 global (March2^-/-) and vascular smooth muscle cell-specific deletion (March2^fl/fl; Tagln^Cre) mice, whereas the AAD pathology was rescued by rAAV9-SM22α-March2 (recombinant adeno-associated virus serotype 9 expressing Flag-tagged March2 under SM22α promoter). March2 interacted with PKM2 (pyruvate kinase M2) to promote K33-linked polyubiquitination. Deficiency of March2 lessened PKM2 dimer-to-tetramer conversion in AAD and overtly exacerbated AAD-induced histone H3K18 lactylation in vascular smooth muscle cells by fostering glucose metabolism reprogramming, thereby promoting p53-driven apoptotic transcriptional response-a hallmark of AAD pathogenesis. TEPP-46, a PKM2-specific activator, pronouncedly alleviated March2 deficiency-deteriorated AAD pathology.</p><p><strong>Conclusions: </strong>Our findings demonstrated that March2 is a novel endogenous defender that prevents AAD by inhibiting vascular smooth muscle cell apoptosis, suggesting that March2 represents a potential therapeutic target for AAD.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":16.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613750","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}