Article
|
Open Access
Featured
-
-
Article
| Open AccessThe pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis
Cardiovascular events are the main cause of mortality in patients with metabolic dysfunctionassociated steatohepatitis (MASH). Here, the authors show that lanifibranor improves cardiometabolic health - insulin sensitivity, lipid and glucose metabolism, systemic inflammation and hepatic steatosis.
- Michael P. Cooreman
- , Javed Butler
- & Sven M. Francque
-
Article
| Open AccessSleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes
Sleep disorders increase the risk and mortality of heart disease. Here, the authors show that sleep fragmentation results in elevated copper levels in the male mouse heart and exacerbates myocardial ischemia–reperfusion injury with increased myocardial cuproptosis and apoptosis.
- Na Chen
- , Lizhe Guo
- & E. Wang
-
Article
| Open AccessLncRNA-LncDACH1 mediated phenotypic switching of smooth muscle cells during neointimal hyperplasia in male arteriovenous fistulas
Arteriovenous fistulas are the most common vascular access points for hemodialysis, but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia. Here, the author shows that LncDACH1 regulates NIH through the HSP90/ SRPK1/ AKT signaling axis.
- Zhaozheng Li
- , Yao Zhao
- & Jundong Jiao
-
Article
| Open AccessProtein disulfide isomerase cleaves allosteric disulfides in histidine-rich glycoprotein to regulate thrombosis
Vascular protein disulfide isomerase (PDI) regulates thrombosis and targeting extracellular PDI remains a promising antithrombotic approach. Here, the authors show that PDI cleaves allosteric disulfides on histidine-rich glycoprotein to influence its functions during coagulation and thus fine-tune the kinetics of thrombus formation.
- Keyu Lv
- , Shuai Chen
- & Chao Fang
-
Article
| Open AccessStatins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1
Endothelial dysfunction has been shown to occur in HFpEF and we know that statins can target endothelial dysfunction by inhibiting miR-133a. Here the authors show that statins improve diastolic dysfunction in HFpEF by increasing the levels of a circRNA which, in turns, binds to miR-133a modulating its downstream targets.
- Bin Li
- , Wen-Wu Bai
- & Shuang-Xi Wang
-
Article
| Open AccessGenetic associations of protein-coding variants in venous thromboembolism
Here, the authors perform a large exome-wide study for venous thromboembolism and identify 18 potential risk genes, including 4 new genes, revealing a significant role of rare coding variants, and offering insights into genetic risk factors.
- Xiao-Yu He
- , Bang-Sheng Wu
- & Jin-Tai Yu
-
Article
| Open AccessS100A8/A9 as a prognostic biomarker with causal effects for post-acute myocardial infarction heart failure
Heart failure is the most prevalent complication of acute myocardial infarction. Here, the authors show that circulating S100A8/A9 is a robust predictor and potentially causal medicator for heart failure post-acute myocardial infarction, as such could serve as a promising drug target for cardioprotection.
- Jie Ma
- , Yang Li
- & Yulin Li
-
Article
| Open AccessEpigenetic modulators link mitochondrial redox homeostasis to cardiac function in a sex-dependent manner
Efforts to treat heart failure with antioxidants have failed. Here, authors reveal a robust sex-dependent endogenous defense against oxidative damage and demonstrate antioxidative treatment’s efficacy solely in subjects with inadequate redox capacity.
- Zaher ElBeck
- , Mohammad Bakhtiar Hossain
- & Christer Betsholtz
-
Article
| Open AccessElevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity
Dysmetabolism of triglyceride-rich lipoproteins is considered a shared risk factor for cardiometabolic diseases, but their associations with cardiometabolic multimorbidity have not been fully understood. Here, the authors show that elevated levels of remnant cholesterol and triglycerides were observationally and genetically associated with a higher risk of cardiometabolic multimorbidity.
- Yimin Zhao
- , Zhenhuang Zhuang
- & Tao Huang
-
Article
| Open AccessALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice
Cardiac macrophage contributes to the onset of cardiac fibrosis, but the underneath mechanisms remain unclear. Here the authors show that mouse cardiac macrophages from circulating monocytes may trans-differentiate into myofibroblast under hypertensive conditions for fibrosis development, with an AKLBH5/IL11 molecular axis modulating this macrophage-to-myofibroblast transition.
- Tao Zhuang
- , Mei-Hua Chen
- & Cheng-Chao Ruan
-
Article
| Open AccessTargeting HDAC6 to treat heart failure with preserved ejection fraction in mice
HFpEF has few effective treatments. Here, the authors show that inhibition of histone deacetylase 6 (HDAC6) with TYA-018 reverses established HFpEF symptoms in mice, comparably to the use of a sodium-glucose cotransporter 2 inhibitor; highlighting HDAC6 as a potential target to treat HFpEF.
- Sara Ranjbarvaziri
- , Aliya Zeng
- & Jin Yang
-
Article
| Open AccessProtective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury
Nanozymes can be used for targeting reactive oxygen species (ROS) to alleviate myocardial ischemia/reperfusion (I/R) injury, but hindered by catalytic performance and toxicity concerns. Here the authors report multienzyme-mimicking and biocompatible Pt-NC single-atom nanozymes as an efficient ROS decomposer for restoring cellular homeostasis and mitigating apoptotic progression after I/R injury.
- Tianbao Ye
- , Cheng Chen
- & Chengxing Shen
-
Article
| Open AccessPro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence
Ferroptosis is a novel form of regulated cell death associated with lipid oxidation. Here, the authors demonstrate that the proferroptosis signal is activated and drives vascular aging by inducing senescence in vascular smooth muscle cells.
- Di-Yang Sun
- , Wen-Bin Wu
- & Pei Wang
-
Article
| Open AccessPalmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling
Patients with Type 2 Diabetes Mellitus are increasingly susceptible to atherosclerotic plaque vulnerability. Here, the authors show that elevated palmitic acid levels are linked to increased atherosclerotic plaque vulnerability.
- Xiqiang Wang
- , Ling Zhu
- & Zhongwei Liu
-
Article
| Open AccessResolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease
Specialized pro-resolving mediators (SPM) are involved in the reprogramming of immune responses. Here the authors show that resolvin (RvT) 4 limits the progression of vascular disease in mouse models of arthritis exacerbated atherosclerotic inflammation.
- Mary E. Walker
- , Roberta De Matteis
- & Jesmond Dalli
-
Article
| Open AccessCongenital heart disease detection by pediatric electrocardiogram based deep learning integrated with human concepts
Congenital heart disease is life threatening, and its screening is complex and costly. Here, authors use AI to detect the disease based on pediatric electrocardiogram, suggesting superior performance over cardiologists.
- Jintai Chen
- , Shuai Huang
- & Huiying Liang
-
Article
| Open AccessA drug-free cardiovascular stent functionalized with tailored collagen supports in-situ healing of vascular tissues
The efficacy of drug-eluting stents remains limited due to delayed reendothelialization, impaired intimal remodeling, and potentially increased late restenosis. Here the authors propose a one-produces-multi stent coating, a drug-free strategy that supports in situ healing of vascular tissues, as demonstrated in rabbit and porcine models.
- Haoshuang Wu
- , Li Yang
- & Yunbing Wang
-
Article
| Open AccessDNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts
This study uncovers a critical link between DNMT3A-driven CHIP and heart failure and, in particular, it shows that DNMT3A inactivation in monocytes boosts the release of HB-EGF, which activates fibroblasts inducing diffuse fibrosis in the heart.
- Mariana Shumliakivska
- , Guillermo Luxán
- & Stefanie Dimmeler
-
Article
| Open AccessLarge scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development
The pathobiology of heart failure (HF) is incompletely understood. The authors identify 37 circulating proteins and 5 protein modules associated with HF risk, with several demonstrating causal effects on HF, risk factors, or cardiac dysfunction by Mendelian randomization analysis.
- Amil M. Shah
- , Peder L. Myhre
- & Bing Yu
-
Article
| Open AccessAmyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity
Epidemiological evidence has identified associations among obesity, Alzheimer’s disease, and cardiovascular disease. Here, the authors report that adipose tissue releases amyloid beta 42 (Aβ42) and that antagonizing Aβ42 protects cardiac function in obesity murine models.
- Liam G. Hall
- , Juliane K. Czeczor
- & Sean L. McGee
-
Article
| Open Access15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β
Specialised pro-resolving lipid mediators can reduce inflammatory responses and may be active in lymphedema. Here the authors show that in a mouse model 15-LO derived lipid mediators are reduced during inflammation and that a lack of the 15-LO producing enzyme aggravated disease and addition of 15-LO enzyme or Treg cells reduced disease.
- A. Zamora
- , M. Nougué
- & B. Garmy-Susini
-
Article
| Open AccessSpatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction
Enhancing vascularization to improve cardiac disease outcomes is a therapeutic approach with limited success. Here, the authors show that cardiac repair is governed by spatiotemporally regulated programs and underline the signaling mechanisms driving vascular deterioration.
- Lin Wei Tung
- , Elena Groppa
- & Fabio Rossi
-
Article
| Open AccessGenome-wide association study meta-analysis of blood pressure traits and hypertension in sub-Saharan African populations: an AWI-Gen study
Hypertension is a major risk factor for cardiovascular disease prevalent in Africa. Here the authors report a genome-wide study providing insights into the genetics and physiology of blood pressure variation in African populations.
- Surina Singh
- , Ananyo Choudhury
- & Michèle Ramsay
-
Article
| Open AccessAtherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation
Accumulation of lipid-laden macrophages in the arterial wall is a critical step in atherosclerosis. Here, the authors show that downregulation of Zeb1 in macrophages promotes lipid accumulation and atherosclerotic plaque formation while its restoration with macrophage-targeted nanoparticles reverses these effects.
- M. C. Martinez-Campanario
- , Marlies Cortés
- & Antonio Postigo
-
Article
| Open AccessDietary circadian rhythms and cardiovascular disease risk in the prospective NutriNet-Santé cohort
The relation between daily meal and fasting timing with cardiovascular disease incidence remains unclear. Here, authors show that a later daily meal timing is associated with increased cardiovascular disease risk, especially in women. This study suggests that adopting earlier daily eating patterns may be beneficial for cardiovascular prevention.
- Anna Palomar-Cros
- , Valentina A. Andreeva
- & Bernard Srour
-
Article
| Open AccessModeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells
Cardiac fibroblasts play an essential role in heart development. Here Fernandes et al. describe a human pluripotent stem cell-derived epicardial organoid system to investigate the role of fibroblasts in cardiovascular development and disease.
- Ian Fernandes
- , Shunsuke Funakoshi
- & Gordon Keller
-
Article
| Open AccessGRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis
Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.
- Qiang Zhu
- , Matthew E. Combs
- & Joan M. Taylor
-
Article
| Open AccessChoroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment
In patients with CKD, there is an unmet need for biomarkers that reliably track kidney injury. Here, in a series of prospective studies, the authors show that retinal OCT metrics reflect kidney injury, are modified by treatments for kidney disease and can predict future decline of kidney function.
- Tariq E. Farrah
- , Dan Pugh
- & Neeraj Dhaun
-
Article
| Open AccessSelenoprotein deficiency disorder predisposes to aortic aneurysm formation
Aortic aneurysms have a heritable basis. Here, the authors report that a selenoprotein deficiency disorder due to mutations in SECISBP2, causes oxidative stress-mediated aortic cell death, predisposing to thoracic aortic aneurysm formation.
- Erik Schoenmakers
- , Federica Marelli
- & Krishna Chatterjee
-
Article
| Open AccessGenome-wide association analysis of left ventricular imaging-derived phenotypes identifies 72 risk loci and yields genetic insights into hypertrophic cardiomyopathy
Changes of left ventricular structure are used to predict morbidity and mortality in cardiovascular diseases. Here the authors conducted a study using advanced deep learning technology to analyze left ventricular regional wall thickness (LVRWT) in a large population, identifying 72 significant genetic loci linked to LVRWT traits.
- Caibo Ning
- , Linyun Fan
- & Xiaoping Miao
-
Article
| Open AccessReduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension
It is unknown whether unrepaired DNA damage in lung endothelial cells causes persistent pulmonary arterial hypertension. Here, the authors combine oxidative stress with impaired BMPR2 signaling to link a reduction in FOXF1 to unrepaired DNA damage and impaired regeneration of normal endothelium.
- Sarasa Isobe
- , Ramesh V. Nair
- & Marlene Rabinovitch
-
Article
| Open AccessCis-trans isomerization of peptoid residues in the collagen triple-helix
The cis-peptide bond is rare in natural proteins and its impact on protein folding is elusive. Here the authors break the conventional understanding that cis-amide-favoring residues destabilize proteins, elucidate the principles of peptoid cis-trans isomerization in collagen folding, and showcase the use of cis-amide-favoring residues in building programmable and functional peptidomimetics.
- Rongmao Qiu
- , Xiaojing Li
- & Yang Li
-
Article
| Open AccessProtective effects of macrophage-specific integrin α5 in myocardial infarction are associated with accentuated angiogenesis
During myocardial infarction, cardiac macrophages expand, become activated and play an important role in cardiac repair and remodelling. Here the authors show that integrin α5 is upregulated in infarct macrophages and contributes to myocardial repair, triggering an angiogenic phenotype and protecting from adverse remodelling.
- Ruoshui Li
- , Bijun Chen
- & Nikolaos G. Frangogiannis
-
Article
| Open AccessEicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction
Systemic inflammation is recognized as a central pathobiologic feature in heart failure with preserved ejection fraction (HFpEF). Here, the authors report 70 pro- and anti-inflammatory eicosanoid and eicosanoid-related metabolites associated with HFpEF status.
- Emily S. Lau
- , Athar Roshandelpoor
- & Jennifer E. Ho
-
Article
| Open AccessMutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Vein of Galen malformations (VOGMs) are severe congenital brain arteriovenous malformations. Here the authors work to elucidate the pathogenesis of VOGMs by performing an integrated analysis of 310 VOGM proband family exomes and 336,326 human cerebrovasculature single-cell transcriptomes to identify mutations of key signaling regulators.
- Shujuan Zhao
- , Kedous Y. Mekbib
- & Kristopher T. Kahle
-
Article
| Open AccessEnhanced pericyte-endothelial interactions through NO-boosted extracellular vesicles drive revascularization in a mouse model of ischemic injury
Treatment alternatives are not available for a significant portion of critical limb ischemia patients. Here, the authors show a strategy to engineer mesenchymal stem cells-derived extracellular vesicles to induce revascularization in mice.
- Ling Guo
- , Qiang Yang
- & Min Feng
-
Article
| Open AccessGut butyrate-producers confer post-infarction cardiac protection
Here, Chen et. al. characterize the relationship between the gut microbiota and plasma metabolite changes in the context of ST-elevation myocardial infarction (STEMI), unveiling a role of butyrate-producing bacteria and their ketogenesis in post-STEMI cardiac repair, a finding validated in nonhuman primate and mouse models. They show that butyrate supplementation reduces myocardial infarction severity in mice, underscoring the significance of butyrate-producing bacteria and beta-hydroxybutyrate in improving post-MI outcomes.
- Hung-Chih Chen
- , Yen-Wen Liu
- & Patrick C. H. Hsieh
-
Article
| Open AccessPoor sleep and shift work associate with increased blood pressure and inflammation in UK Biobank participants
Circadian disruption is linked to increased blood pressure and heart disease risk. Here, the authors show a positive association between circadian disruption and blood pressure (SBP/DBP) regulation in males and females irrespective of age, weight and inflammatory status.
- Monica Kanki
- , Artika P. Nath
- & Morag J. Young
-
Article
| Open AccessHealthy dietary patterns and the risk of individual chronic diseases in community-dwelling adults
Dietary patterns have been linked to a limited number of major chronic diseases. Here, the authors show greater adherence to healthy dietary patterns, especially Alternate Mediterranean Diet, is associated with a lower risk of most of the 48 tested chronic diseases.
- Xianwen Shang
- , Jiahao Liu
- & Mingguang He
-
Article
| Open AccessActivation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination
Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.
- Malika Aid
- , Kathryn E. Stephenson
- & Dan H. Barouch
-
Article
| Open AccessMYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM)
Arrhythmogenic cardiomyopathy is an untreatable heart muscle disease and a common cause of sudden cardiac death in young athletes. The authors show a link between actomyosin dysregulation and cardiac dysfunction by studying nonsense PKP2 mutants classified as pathogenic to identify a potential treatment.
- Nieves García-Quintáns
- , Silvia Sacristán
- & Juan A. Bernal
-
Article
| Open AccessIn vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice
The assessment of selective therapeutics targeted to treat altered vasoactivity, a major characteristic of cardiovascular and oncological diseases, is still challenging due to unknown whole-body selectivity. Here the authors demonstrate that photoacoustic tomography has the potential to capture significant acute vasodilation of major arteries and vasculature selectivity.
- Kristie Huda
- , Dylan J. Lawrence
- & Carolyn L. Bayer
-
Article
| Open AccessMechanically induced pyroptosis enhances cardiosphere oxidative stress resistance and metabolism for myocardial infarction therapy
Therapeutic options for myocardial infarction therapy remain limited. Here the authors report the application of an optimized liquid crystal substrate in the mass production and effective preconditioning of cardiospheres, which could generate cardiospheres with improved cell bioactivity and resistance to oxidative stress for myocardial infarction therapy.
- Yingwei Wang
- , Qi Li
- & Zheng Wu
-
Article
| Open AccessHypersensitive MR angiography based on interlocking stratagem for diagnosis of cardiac-cerebral vascular diseases
Current contrast-enhanced magnetic resonance angiography approaches are sub-optimal. Here the authors present a hypersensitive MR angiography strategy based on interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd), enabling sophisticated micro-vessel angiography of cardiac-cerebrovascular diseases with ultrahigh resolution.
- Peisen Zhang
- , Junwei Cheng
- & Yi Hou
-
Article
| Open AccessEndothelial Sp1/Sp3 are essential to the effect of captopril on blood pressure in male mice
Hypertension is the leading risk factor for cardiovascular disease, which represents the top cause of morbidity and mortality worldwide. Here, the authors show deletion of endothelial Sp1 and Sp3 leads to a disruption in endothelium-dependent vasodilation and the onset of hypertension, which abolishes the beneficial actions of captopril.
- Hanlin Lu
- , Xiuxin Jiang
- & Wencheng Zhang
-
Article
| Open AccessEvidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
TMAO is known to be atherothrombotic. Here the authors show that i) kidney function is the main determinant of serum TMAO, ii) TMAO increases kidney scarring with TGF-β1 signalling and iii) anti-diabetic drugs with reno-protective properties such as GLP1R agonists reduce plasma TMAO.
- Petros Andrikopoulos
- , Judith Aron-Wisnewsky
- & Marc-Emmanuel Dumas
-
Article
| Open AccessSinus venosus adaptation models prolonged cardiovascular disease and reveals insights into evolutionary transitions of the vertebrate heart
Nr2fs are conserved transcription factors that regulate atrial chamber and venous development. Here, the authors use adult zebrafish nr2f1a mutants to investigate compensatory remodeling of the inflow tract and hypotheses of cardiac evolution.
- Jacob T. Gafranek
- , Enrico D’Aniello
- & Joshua S. Waxman
-
Article
| Open AccessCis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia
Preeclampsia is the leading cause of maternal and fetal mortality worldwide. Here, the authors show that cis P-tau is a central circulating etiologic driver in preeclampsia and that the stereo-specific antibody targeting cis P-tau holds promise for early diagnosis and treatment of the disease.
- Sukanta Jash
- , Sayani Banerjee
- & Surendra Sharma
-
Article
| Open AccessFAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination
The mechanisms underlying vascular smooth muscle cell reprogramming in abdominal aortic aneurism (AAA) remain unclear. Here they show that FAM3A, a metabolic cytokine, serves as a cell fate-shaping regulator of smooth muscle cells to protect against AAA formation.
- Chuxiang Lei
- , Haoxuan Kan
- & Yuehong Zheng