Cardiovascular Research最新文献

{"title":"Physiological and pathological ventricular hypertrophy: a role for cavin-2 mediated Akt regulation.","authors":"Raffaele Coppini, Lucrezia Giammarino, Elisabetta Cerbai","doi":"10.1093/cvr/cvae184","DOIUrl":"10.1093/cvr/cvae184","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1499-1500"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072073","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":"Causal cardiovascular risk factors for dementia - insights from observational and genetic studies.","authors":"Emilie Westerlin Kjeldsen, Ruth Frikke-Schmidt","doi":"10.1093/cvr/cvae235","DOIUrl":"https://doi.org/10.1093/cvr/cvae235","url":null,"abstract":"<p><p>The escalating prevalence of dementia worldwide necessitates preventive strategies to mitigate its extensive health, psychological, and social impacts. As the prevalence of dementia continues to rise, gaining insights into its risk factors and causes become paramount, given the absence of a definitive cure. Cardiovascular disease has emerged as a prominent player in the complex landscape of dementia. Preventing, dyslipidaemia, unhealthy Western type diets, hypertension, diabetes, being overweight, physical inactivity, smoking, and high alcohol intake have the potential to diminish not only cardiovascular disease but also dementia. The purpose of this review is to present our current understanding of cardiovascular risk factors for Alzheimer's disease (AD) and vascular dementia (VaD) by using clinical human data from observational, genetic studies and clinical trials, while elaborating on potential mechanisms. Hypertension and type 2 diabetes surface as significant causal risk factors for both AD and VaD, as consistently illustrated in observational and Mendelian randomization studies. Antihypertensive drugs and physical activity have been shown to improve cognitive function in clinical trials. Important to note is, that robust genome wide associations studies are lacking for VaD, and indeed more and prolonged clinical trials are needed to establish these findings and investigate other risk factors. Trials should strategically target individuals at the highest dementia risk, identified using risk charts incorporating genetic markers, biomarkers, and cardiovascular risk factors. Understanding causal risk factors for dementia will optimise preventive measures, and implementation of well-known therapeutics can halt or alleviate dementia symptoms if started early. Needless to mention is that future health policies should prioritise primordial prevention from early childhood to prevent risk factors from even occurring in the first place. Together, understanding the role of cardiovascular risk factors in dementia, improving GWASs for VaD, and advancing clinical trials are crucial steps in addressing this significant public health challenge.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582125","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":"Neuroimmune cross-talk in heart failure.","authors":"Sabrina Montuoro, Francesco Gentile, Alberto Giannoni","doi":"10.1093/cvr/cvae236","DOIUrl":"https://doi.org/10.1093/cvr/cvae236","url":null,"abstract":"<p><p>Heart failure (HF) is characterized by autonomic nervous system (ANS) imbalance and low-grade chronic inflammation. The bidirectional relationship between the ANS and immune system (IS) is named \"neuroimmune cross-talk\" (NICT), and is based on common signaling molecules, receptors, and pathways. NICT may be altered in HF, and neuroinflammation seems to be a main driver of HF progression. In HF, heightened sympathetic nerve activity triggers inflammatory cascades that lead to cardiomyocyte death and myocardial interstitial fibrosis. Concurrently, parasympathetic withdrawal may impair the cholinergic anti-inflammatory pathway, with a less effective immune response to infections or inflammatory events. Additionally, microglial activation and inflammatory molecules contribute to autonomic imbalance by acting on central nuclei and peripheral visceral feedbacks, which in turn promote adverse cardiac remodeling, HF decompensation, and potentially life-threatening arrhythmias. Therefore, neuroinflammation has been identified as a potential target for treatment. Pharmacological antagonism of the neurohormonal system remains the cornerstone of chronic HF therapy. While some drugs used in HF management may have additional benefits due to their anti-inflammatory properties, clinical trials targeting inflammation in patients with HF have so far produced inconclusive results. Nevertheless, considering the pathophysiological relevance of NICT, its modulation seems an appealing strategy to optimize HF management. Current research is therefore investigating novel pharmacological targets for anti-inflammatory drugs, and the immunomodulatory properties of denervation approaches and bioelectronic medicine devices targeting NICT and neuroinflammation in HF. A deeper understanding of the complex relationship between the ANS and IS, as outlined in this review, could therefore facilitate the design of future studies aimed at improving outcomes by targeting NICT in patients with HF.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582130","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":"Nuclear factor of activated T-cells 5 is indispensable for a balanced adaptive transcriptional response of lung endothelial cells to hypoxia.","authors":"Hebatullah Laban, Sophia Siegmund, Katharina Schlereth, Felix A Trogisch, Alia Ablieh, Lennart Brandenburg, Andreas Weigert, Carolina De La Torre, Carolin Mogler, Markus Hecker, Wolfgang M Kuebler, Thomas Korff","doi":"10.1093/cvr/cvae151","DOIUrl":"10.1093/cvr/cvae151","url":null,"abstract":"<p><strong>Aims: </strong>Chronic hypoxia causes detrimental structural alterations in the lung, which may cause pulmonary hypertension and are partially mediated by the endothelium. While its relevance for the development of hypoxia-associated lung diseases is well known, determinants controlling the initial adaptation of the lung endothelium to hypoxia remain largely unexplored.</p><p><strong>Methods and results: </strong>We revealed that hypoxia activates the transcription factor nuclear factor of activated T-cells 5 (NFAT5) and studied its regulatory function in murine lung endothelial cells (MLECs). EC-specific knockout of Nfat5 (Nfat5(EC)-/-) in mice exposed to normobaric hypoxia (10% O2) for 21 days promoted vascular fibrosis and aggravated the increase in pulmonary right ventricular systolic pressure as well as right ventricular dysfunction as compared with control mice. Microarray- and single-cell RNA-sequencing-based analyses revealed an impaired growth factor-, energy-, and protein-metabolism-associated gene expression in Nfat5-deficient MLEC after exposure to hypoxia for 7 days. Specifically, loss of NFAT5 boosted the expression and release of platelet-derived growth factor B (Pdgfb)-a hypoxia-inducible factor 1 alpha (HIF1α)-regulated driver of vascular smooth muscle cell (VSMC) growth-in capillary MLEC of hypoxia-exposed Nfat5(EC)-/- mice, which was accompanied by intensified VSMC coverage of distal pulmonary arteries.</p><p><strong>Conclusion: </strong>Collectively, our study shows that early and transient subpopulation-specific responses of MLEC to hypoxia may determine the degree of organ dysfunction in later stages. In this context, NFAT5 acts as a protective transcription factor required to rapidly adjust the endothelial transcriptome to cope with hypoxia. Specifically, NFAT5 restricts HIF1α-mediated Pdgfb expression and consequently limits muscularization and resistance of the pulmonary vasculature.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1590-1606"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896886","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":"CircARCN1 aggravates atherosclerosis by regulating HuR-mediated USP31 mRNA in macrophages.","authors":"Zhicheng Pan, Jialan Lv, Liding Zhao, Kaidi Xing, Runze Ye, Yuesheng Zhang, Siyuan Chen, Peng Yang, Hailong Yu, Yangkai Lin, Ruobing Li, Dongfei Wang, Juan Fang, Yang Dong, Jianpeng Sheng, Xiaolin Wang, Ge Shan, Shan Zhang, Hongqiang Cheng, Qingbo Xu, Xiaogang Guo","doi":"10.1093/cvr/cvae148","DOIUrl":"10.1093/cvr/cvae148","url":null,"abstract":"<p><strong>Aims: </strong>Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis.</p><p><strong>Methods and results: </strong>Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE-/- mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κB activation. Interestingly, macrophage accumulation and inflammation in atherosclerotic plaques were markedly decreased when circARCN1 was knocked down with adeno-associated virus in macrophages of ApoE-/- mice, while circARCN1 overexpression in the model exacerbated atherosclerotic lesions.</p><p><strong>Conclusions: </strong>Our findings provide solid evidence macrophagic-expressed circARCN1 plays a role in atherosclerosis development by regulating HuR-mediated USP31 mRNA stability and NF-κB activation, suggesting that circARCN1 may serve as a factor for atherosclerotic lesion formation.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1531-1549"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726951","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":"GWAS breakthroughs: mapping the journey from one locus to 393 significant coronary artery disease associations.","authors":"Rédouane Aherrahrou, Tobias Reinberger, Satwat Hashmi, Jeanette Erdmann","doi":"10.1093/cvr/cvae161","DOIUrl":"10.1093/cvr/cvae161","url":null,"abstract":"<p><p>Coronary artery disease (CAD) poses a substantial threat to global health, leading to significant morbidity and mortality worldwide. It has a significant genetic component that has been studied through genome-wide association studies (GWAS) over the past 17 years. These studies have made progress with larger sample sizes, diverse ancestral backgrounds, and the discovery of multiple genomic regions related to CAD risk. In this review, we provide a comprehensive overview of CAD GWAS, including information about the genetic makeup of the disease and the importance of ethnic diversity in these studies. We also discuss challenges of identifying causal genes and variants within GWAS loci with a focus on non-coding regions. Additionally, we highlight tissues and cell types relevant to CAD, and discuss clinical implications of GWAS findings including polygenic risk scores, sex-specific differences in CAD genetics, ethnical aspects of personalized interventions, and GWAS guided drug development.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1508-1530"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787354","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":"SCUBE2, where are you? Recruitment of SCUBE2 to adherens junctions preserves vascular health and integrity.","authors":"Wendy Stam, Coert Margadant","doi":"10.1093/cvr/cvae182","DOIUrl":"10.1093/cvr/cvae182","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1503-1504"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139419","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":"Intraplatelet miRNA-126 regulates thrombosis and its reduction contributes to platelet inhibition.","authors":"Lu-Jun Zhang, Yang-Xi Hu, Rong-Zhong Huang, Yan-Yan Xu, Shao-Hua Dong, Fang-Hao Guo, Jun-Jun Guo, Jing-Jing Qiu, Zi-Yun Cao, Li-Jiang Wei, Jia-Hao Mao, Ankang Lyu, Jun-Ling Liu, Xian-Xian Zhao, Zhi-Fu Guo, Qing Jing","doi":"10.1093/cvr/cvae138","DOIUrl":"10.1093/cvr/cvae138","url":null,"abstract":"<p><strong>Aims: </strong>MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear.</p><p><strong>Methods and results: </strong>Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading, and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the phosphoinositide 3-kinase/protein kinase B pathway, enhancing platelet activation through activating the integrin αIIbβ3-mediated outside-in signalling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease in platelet activity.</p><p><strong>Conclusion: </strong>Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1622-1635"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431491","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":"Single-nucleus transcriptomics reveals adrenergic and STAT3 signalling in paradoxical low-flow low-gradient-specific cardiomyocyte subclusters: implications for aortic stenosis pathogenesis and treatment.","authors":"Xingbo Xu, Xiaoying Tan, Baolong Cui, Niels B Paul, Manar Elkenani, Bo E Beuthner, Weichao Li, Belal A Mohamed, Moritz Schnelle, Miriam Puls, Elisabeth M Zeisberg, Michael Zeisberg, Tim Beißbarth, Karl Toischer, Gerd Hasenfuß","doi":"10.1093/cvr/cvae137","DOIUrl":"10.1093/cvr/cvae137","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1505-1507"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466414","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 history of science captured in paintings: what modern scientists can learn by studying the history of science?","authors":"Gerard Pasterkamp, Tomasz J Guzik","doi":"10.1093/cvr/cvae209","DOIUrl":"https://doi.org/10.1093/cvr/cvae209","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"120 13","pages":"e51-e53"},"PeriodicalIF":10.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575095","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}