Featured
-
-
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
-
Article
| Open AccessGut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study
Here, using amplicon sequencing and metabolomics in a large multi-country cohort, the authors find that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries.
- Gertrude Ecklu-Mensah
- , Candice Choo-Kang
- & Lara R. Dugas
-
Article
| Open AccessEnvironmental and genetic predictors of human cardiovascular ageing
Cardiovascular ageing is characterised by a progressive decline in function, which contributes to multi-morbidity. Here, the authors use machine learning to predict biological age and identify key genetic risk factors.
- Mit Shah
- , Marco H. de A. Inácio
- & Declan P. O’Regan
-
Article
| Open AccessThin, soft, wearable system for continuous wireless monitoring of artery blood pressure
Continuous monitoring of arterial blood pressure is limited by bulky connecting systems and poor interfacial contact. Here, Li et al. report a wearable thin, soft, miniaturized system that integrates sensing, active pressure adaptation, and signal processing for improved performance and accuracy.
- Jian Li
- , Huiling Jia
- & Xinge Yu
-
Article
| Open AccessIRX2 regulates angiotensin II-induced cardiac fibrosis by transcriptionally activating EGR1 in male mice
Cardiac fibrosis is a common feature of chronic heart failure, and the mechanisms of cardiac fibrosis are unclear. Here, the authors show that iroquois homeobox 2 (IRX2) regulates the early growth response factor 1 (EGR1) pathway upon fibrotic stimulation and drives cardiac fibrosis.
- Zhen-Guo Ma
- , Yu-Pei Yuan
- & Qi-Zhu Tang
-
Article
| Open AccessSmall molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels
Branched chain ketoacid dehydrogenase kinase (BDK) inhibits the activity of branched chain ketoacid dehydrogenase and branched chain amino acid degradation, implicated in several diseases. Here, the authors discover a BDK inhibitor and degrader that shows efficacy in rodent metabolism and heart failure models, as well as another class of BDK inhibitors that stabilizes BDK.
- Rachel J. Roth Flach
- , Eliza Bollinger
- & Kevin J. Filipski
-
Article
| Open AccessNon-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value
Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. Here, the authors use non-invasive atrial electromechanical assessment during AF to identify early remodeling changes associated with underlying myopathy, which in the clinic decrease the probability of acute and mid-term successful rhythm control.
- Daniel Enríquez-Vázquez
- , Jorge G. Quintanilla
- & David Filgueiras-Rama
-
Article
| Open AccessGenetic insights into resting heart rate and its role in cardiovascular disease
The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.
- Yordi J. van de Vegte
- , Ruben N. Eppinga
- & Pim van der Harst
-
Article
| Open AccessGenetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy
Previous studies suggested a role for CARD9 pathway in atherosclerosis but the underlying mechanisms remain poorly understood. Here, the authors show that the pro-atherogenic effects of Card9 deficiency are mediated by CD36-dependent defective autophagy that can be reversed by rapamycin and metformin.
- Yujiao Zhang
- , Marie Vandestienne
- & Hafid Ait-Oufella
-
Article
| Open AccessLysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34
iPLA2β produces lipid mediators and induces nuclear shrinkage in caspase-independent cell death. Here, the authors show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death mediated through GPR34 in pressure-overloaded mouse hearts, leading to cardiac dysfunction.
- Ryuta Sugihara
- , Manabu Taneike
- & Kinya Otsu
-
Article
| Open AccessCysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR)
Oxidation of ryanodine receptor calcium channels play a critical role in the onset of many cardiac diseases. Here, authors identify specific amino acids that cause ryanodine receptor malfunction during oxidative stress.
- Roman Nikolaienko
- , Elisa Bovo
- & Aleksey V. Zima
-
Article
| Open AccessEzh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI
Modulating pro-inflammatory immune cell kinetics after myocardial infarction is a critical step to prevent heart dysfunction. In this study, the authors show that Ezh2 pharmacological inhibition, acting as an epigenetic checkpoint in monocytes and macrophages, prevents myocardial infarction-induced cardiac dysfunction.
- Julie Rondeaux
- , Déborah Groussard
- & Sylvain Fraineau
-
Article
| Open AccessMacrophage-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes atherosclerosis in male mice
Hypercholesterolemia and vascular inflammation both contribute to the pathogenesis of atherosclerosis, but how hypercholesterolemia initiates vascular inflammation is not fully understood. Here the authors report that crosstalk between macrophages and endothelial cells mediated by the cholesterol metabolite 27-hydroxycholesterol drives vascular inflammation and contributes to atherosclerosis in male mice.
- Liming Yu
- , Lin Xu
- & Philip W. Shaul
-
Article
| Open AccessElastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease
Pulmonary hypertension due to left heart disease is characterized by pulmonary arterial stiffening that results from extracellular matrix remodeling. Here, the authors show that elastin stabilization improves arterial biomechanics and attenuates pulmonary hypertension.
- Mariya M. Kucherenko
- , Pengchao Sang
- & Christoph Knosalla
-
Article
| Open AccessMislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3
The authors show that loss-of-interaction with the nuclear importer, TNPO3, causes cytoplasmic mislocalization of RBM20 variants linked to severe cases of dilated cardiomyopathy. Restoring their nuclear localization alleviates the disease phenotype.
- Julia Kornienko
- , Marta Rodríguez-Martínez
- & Lars M. Steinmetz
-
Article
| Open AccessGenome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure
Here, the authors perform a large-scale meta-analysis of genome-wide association studies and cis-MR proteomics to identify protein biomarkers and drug targets for heart failure.
- Danielle Rasooly
- , Gina M. Peloso
- & Juan P. Casas
-
Article
| Open AccessAcute stress induces long-term metabolic, functional, and structural remodeling of the heart
Takotsubo disease, a stress induced cardiomyopathy mimicking acute coronary syndrome, increases the risk of heart failure and cardiac death. The authors show here that heart function and structure keep on deteriorating continuously after a single acute stress, this snowball effect being triggered by abnormalities incardiac metabolism.
- Thulaciga Yoganathan
- , Mailyn Perez-Liva
- & Bertrand Tavitian
-
Article
| Open AccessPractical intelligent diagnostic algorithm for wearable 12-lead ECG via self-supervised learning on large-scale dataset
Intelligent diagnostic algorithms for ECG are becoming increasingly important to reduce the workload of cardiologists, enable telemedicine and real-time monitoring. Here, the authors show a model based on self-supervised learning that can classify 60 diagnostic terms for ECG.
- Jiewei Lai
- , Huixin Tan
- & Wei Yang
-
Article
| Open AccessStriated muscle-specific base editing enables correction of mutations causing dilated cardiomyopathy
Dilated cardiomyopathy is the second most common cause for heart failure. Here the authors combine CRISPR base editors with the muscle-targeting viral vector AAVMYO to repair patient mutations in the cardiac splice factor Rbm20 in two mouse models.
- Markus Grosch
- , Laura Schraft
- & Lars M. Steinmetz
-
Article
| Open AccessTisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice
Cardiac I/R injury is a deleterious issue in the clinic. Here, the authors show that Tisp40 facilitates HBP flux and protein O-GlcNAcylation through binding to the promoter of GFPT1, thereby preventing cardiac I/R injury.
- Xin Zhang
- , Can Hu
- & Qi-Zhu Tang
-
Article
| Open AccessSERCA2 phosphorylation at serine 663 is a key regulator of Ca2+ homeostasis in heart diseases
Despite advances in cardioprotection, new therapeutic strategies precluding ischemia-reperfusion injury of patients are still needed. Here, the authors show that preventing serine 663 phosphorylation of SERCA2, significantly increases its activity and protects against cell death, by counteracting cytosolic and mitochondrial Ca2+ overload.
- Fabrice Gonnot
- , Laura Boulogne
- & Ludovic Gomez
-
Article
| Open AccessElevated plasma complement factor H related 5 protein is associated with venous thromboembolism
Improved biomarker-based tools for diagnosis and risk prediction of venous thromboembolism (VTE) are needed. Here, the authors show that Complement Factor H Related 5 protein, a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker in 5 independent cohorts.
- Maria Jesus Iglesias
- , Laura Sanchez-Rivera
- & Jacob Odeberg
-
Article
| Open AccessGalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy
Kasiewicz et al. describe a structure-guided rational design approach to optimize a new GalNAc-Lipid nanoparticle that enables delivery of a base editing therapy in both low-density lipoprotein receptor-deficient and wild-type nonclinical models.
- Lisa N. Kasiewicz
- , Souvik Biswas
- & Andrew M. Bellinger
-
Article
| Open AccessStructure of dimeric lipoprotein lipase reveals a pore adjacent to the active site
LPL hydrolyzes triglycerides from lipoproteins. LPL can adopt many oligomeric forms. Here, the authors solve a 3.9 Å cryoEM structure of the previously uncharacterized LPL dimer. Key features include a C-terminal dimerization interface and a hydrophobic pore next to the active site.
- Kathryn H. Gunn
- & Saskia B. Neher
-
Article
| Open AccessAGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling
Thoracic aortic aneurysm (TAA) causes many sudden deaths each year, however, no effective drug treatment is available. Here, the authors show that AGGF1 protein therapy attenuates TAA in three different mouse models through integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signalling.
- Xingwen Da
- , Ziyan Li
- & Qing K. Wang
-
Article
| Open AccessRPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function
RPL3L is a paralog of the ribosomal protein RPL3 and specifically expressed in heart and skeletal muscle. Here, the authors show that RPL3L-containing ribosomes regulate translation elongation dynamics especially for the transcripts related to cardiac muscle contraction.
- Chisa Shiraishi
- , Akinobu Matsumoto
- & Keiichi I. Nakayama
-
Article
| Open AccessIDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart
Protein targets that are affected by ROS and underly impaired inotropic effects in the heart are largely unknown. Here, the authors identify the γ-subunit of IDH3 as a redox switch linking oxidative stress to impaired metabolism and heart function.
- Maithily S. Nanadikar
- , Ana M. Vergel Leon
- & Dörthe M. Katschinski
-
Article
| Open AccessExtracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice
Extracellular vesicle therapy has shown great potential for the treatment of myocardial infarction. Here, the authors show a silicate biomaterials-based approach to engineer extracellular vesicles from endothelial progenitor cells with high yield and bioactivity for treating myocardial infarction.
- Bin Yu
- , Hekai Li
- & Caiwen Ou
-
Article
| Open AccessAssociations between mental health, blood pressure and the development of hypertension
Mental and cardiovascular health interact in complex ways. Here, the authors demonstrate an association of blood pressure with depressive symptoms, well-being, and emotion-related brain activity that may be relevant to the development of hypertension.
- H. Lina Schaare
- , Maria Blöchl
- & Arno Villringer
-
Article
| Open AccessMEK inhibition reduced vascular tumor growth and coagulopathy in a mouse model with hyperactive GNAQ
Life-threatening vascular tumors can be associated with uncontrolled activity of the guanine nucleotide-binding protein subunit alpha (Gαq). Here, the authors develop a murine model for these tumors and show that MEK inhibition prevents formation of vascular lesions and improves survival.
- Sandra Schrenk
- , Lindsay J. Bischoff
- & Elisa Boscolo
-
Article
| Open AccessP2X3 receptor antagonism attenuates the progression of heart failure
Despite medications, heart failure worsens with time with many patients dying within five years of diagnosis. Here the authors show that blocking purinergic receptors in the carotid body stops heart failure progression, improves its function, reduces sleep apneas and systemic inflammation in male rats.
- Renata M. Lataro
- , Davi J. A. Moraes
- & Julian F. R. Paton
-
Article
| Open AccessA defect in mitochondrial protein translation influences mitonuclear communication in the heart
The heart requires high levels of mitochondria to sustain function, and mitochondrial stressors can be transmitted to the nucleus and reprogram metabolism. Here, the authors show that a mitochondrial ribosomal protein is important for heart development in mice by increasing nuclear Klf15 expression.
- Feng Gao
- , Tian Liang
- & Jinghai Chen
-
Article
| Open AccessFibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice
Although the role of FGFs in cardiovascular disease has attracted extensive attention, the potential role of FGF18 in pathological cardiac hypertrophy remains unknown. Here, the authors show the cardioprotective effect of FGF18 is mediated by maintaining redox homeostasis through FYN/Nox4 signaling.
- Gen Chen
- , Ning An
- & Xu Wang
-
Article
| Open AccessRetinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice
The current challenges for diabetic cardiomyopathy (DCM) are unclear mechanisms and no effective therapy in clinics. Here, the authors found that the decrease of cardiac retinol dehydrogenase 10 in type 2 diabetes leads to retinol metabolism disorder, cardiac lipid toxicity and cardiomyopathy development, suggesting that correcting the imbalance of cardiac retinol metabolism may be an effective strategy for the treatment of DCM.
- Yandi Wu
- , Tongsheng Huang
- & Weibin Cai
-
Article
| Open AccessDefects in placental syncytiotrophoblast cells are a common cause of developmental heart disease
Placental dysfunction can affect heart development, but the prevalence of this causality has not been well established. Here, the authors use mouse genetic tools to show that the placenta may constitute a significant source of congenital heart defects.
- Bethany N. Radford
- , Xiang Zhao
- & Myriam Hemberger
-
Article
| Open AccessThe KLF7/PFKL/ACADL axis modulates cardiac metabolic remodelling during cardiac hypertrophy in male mice
Myocardial substrate metabolism in cardiac hypertrophy or heart failure shifts from fatty acid oxidation to a greater reliance on glycolysis. Here, the authors show that KLF7 can simultaneously regulate key enzymes in glycolysis and fatty acid oxidation to mitigate metabolic imbalance during cardiac hypertrophy.
- Cao Wang
- , Shupei Qiao
- & Weiming Tian
-
Article
| Open AccessGSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis
Macrophages have been shown to have an important function in atherosclerosis. Here the authors show that, in human atherosclerotic plaques and mouse models, GSDME and pyroptosis promote atherosclerosis and inhibition of these pathways could reduce pathology associated with atherosclerotic disease.
- Yuanyuan Wei
- , Beidi Lan
- & Yue Wu
-
Article
| Open AccessMolecular mechanisms of coronary artery disease risk at the PDGFD locus
Genes encode risk for coronary disease, identifying how they function is critical to developing new therapies. In work reported the authors have identified one culprit gene, PDGFD, and studied how it functions to promote disease risk.
- Hyun-Jung Kim
- , Paul Cheng
- & Thomas Quertermous
-
Article
| Open AccessVGLL3 is a mechanosensitive protein that promotes cardiac fibrosis through liquid–liquid phase separation
Heart fibrosis involves a feedback loop where stiffening increases fibrosis-related gene expression in myofibroblasts. Here authors reveal the mechanosensitive nuclear translocation of VGLL3, where it phase separates and promotes collagen production, and show that its knock-out is protective after myocardial infarction.
- Yuma Horii
- , Shoichi Matsuda
- & Michio Nakaya
-
Article
| Open AccessQuantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment
Measuring proteomic subfractions of HDL can help during cardiovascular risk assessment. Here, the authors show, using a Nanoparticle-Gated Electrokinetic Membrane Sensor, the efficacy of Paroxonase 1 on HDL in its ability to diagnose cardiovascular disease compared to other commonly used methods.
- Sonu Kumar
- , Nalin Maniya
- & Hsueh-Chia Chang
-
Article
| Open AccessMolecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke
Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide but current drug therapeutics show important limitations. Here, the authors exploit a selfpropelling nano-penetrator with high fuel loading and controllable motion which is molecularly co-assembled using a photothermal photosensitizer and a photothermal-activable NO donor.
- Hongyuan Zhang
- , Zhiqiang Zhao
- & Cong Luo
-
Article
| Open AccessBMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases
Different location of adipose tissue may have different consequences to cardiometabolic risk. Here the authors report that deep learning enabled accurate prediction of specific adipose tissue volumes, and that after adjustment for BMI, visceral adiposity was associated with increased risk of cardiometabolic disease, while gluteofemoral adiposity was associated with reduced risk.
- Saaket Agrawal
- , Marcus D. R. Klarqvist
- & Amit V. Khera
-
Article
| Open AccessActin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations
Lamin A/C gene mutations cause dilated cardiomyopathy associated with cofilin-1 phosphorylation and actin destabilization. Here, the authors show that phosphorylated cofilin-1 blunts the MRTF-A/SRF axis, leading to decreased tubulin acetylation and altered cardiac structure and function.
- Caroline Le Dour
- , Maria Chatzifrangkeskou
- & Antoine Muchir
-
Article
| Open AccessAMPKα2 controls the anti-atherosclerotic effects of fish oils by modulating the SUMOylation of GPR120
Consuming fish oil is linked to reduced risk of cardiovascular disease in some populations, but the effects are not consistent across studies. Here the authors report that smooth muscle cell AMPKα2 is required for the protective effects of fish oil on atherosclerosis in mice, and acts via post-translational regulation of the fatty acid receptor GPR120.
- Cheng-hui Yan
- , Hai-Wei Liu
- & Ya-ling Han
-
Article
| Open AccessTargeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction
Therapeutic interference with the immune response after myocardial infarction holds the potential to close a clinically relevant gap. Here, the authors show that inhibition of a cardiomyocyte-specific ADAM10 / CX3CL1 axis improves post infarction survival and cardiac function by attenuating neutrophil-mediated myocardial damage.
- Erik Klapproth
- , Anke Witt
- & Ali El-Armouche
-
Article
| Open AccessExtracellular traps from activated vascular smooth muscle cells drive the progression of atherosclerosis
Vascular smooth muscle cells (VSMCs) are known for their fate plasticity in atherosclerosis plaque progression. Here, Zhai et al. show that extracellular traps generated from CD68 + VSMCs adversely contribute to plaque progression and highlight their unexpected role in plaque stability by regulating the direction of VSMC trans-differentiation.
- Ming Zhai
- , Shiyu Gong
- & Wenhui Peng
-
Article
| Open AccessGPR174 knockdown enhances blood flow recovery in hindlimb ischemia mice model by upregulating AREG expression
Gpr174 is a regulator of regulatory T cells, which play an important role in angiogenesis after hindlimb ischemia. Here, the authors show GPR174-deficient Tregs promote AREG expression by inhibiting Gαs/cAMP/PKA signal pathway and increasing EGR1 nuclear accumulation to improve angiogenesis and vascular remodeling in response to ischemic injury.
- Jin Liu
- , Lihong Pan
- & Aijun Sun
-
Article
| Open AccessTRPC channels blockade abolishes endotoxemic cardiac dysfunction by hampering intracellular inflammation and Ca2+ leakage
TRPCs, nonselective cation channels, are involved in cardiac contraction and conduction. Here, the authors show that Trpc1/6 deficiency or pharmacological inhibition improves endotoxemic cardiac dysfunction and prolongs survival by prominently suppressing cardiac inflammation and ER Ca2+ release.
- Na Tang
- , Wen Tian
- & Wei Cao