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Mashup Score: 4EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis | Circulation Research - 1 day(s) ago
BACKGROUND: EPHB4 (ephrin receptor B4) and the RASA1 (p120 Ras GTPase-activating protein) are necessary for the development of lymphatic vessel (LV) valves. However, precisely how EPHB4 and RASA1 regulate LV valve development is unknown. In this study, we examine the mechanisms by which EPHB4 and RASA1 regulate the development of LV valves. METHODS: We used LV-specific inducible EPHB4-deficient mice and EPHB4 knockin mice that express a form of EPHB4 that is unable to bind RASA1 yet retains protein tyrosine kinase activity (EPHB4 2YP) to study the role of EPHB4 and RASA1 in LV valve development in the embryo and LV valve maintenance in adults. We also used human dermal lymphatic endothelial cells in vitro to study the role of EPHB4 and RASA1 as regulators of LV valve specification induced by oscillatory shear stress, considered the trigger for LV valve specification in vivo. RESULTS: LV valve specification, continued valve development postspecification, and LV valve maintenance were bl
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet
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Mashup Score: 2Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation | Circulation Research - 1 day(s) ago
BACKGROUND: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor). Given the proinflammatory function of dissociated CRP and the important role of inflammation in the pathogenesis of AS, we investigated whether shear stress can modify CRP conformation and induce inflammatory effects relevant to AS. METHODS: To determine the effects of pathological shear rates on the function of human CRP, pCRP was subjected to pathophysiologically relevant shear rates and analyzed using biophysical and biochemical methods. To investigate the effect of shear on CRP conformation in vivo, we used a mouse model of arterial stenosis. Levels of mCRP and pCRP wer
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Zeller et al found #CRP senses changes in blood flow through a narrowed aortic #valve, triggering #inflammation that worsens valve narrowing. Learn how this vicious cycle can make aortic valve disease more severe https://t.co/TnZYQEELDT @DrXiaweiWang @BakerResearchAu https://t.co/5YwHgW8Lrl
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Mashup Score: 59Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF | Circulation Research - 1 day(s) ago
BACKGROUND: Metabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis of HF with preserved ejection fraction (HFpEF) is poorly understood. METHODS: In a mouse model of HFpEF, induced by high-fat diet and Nω-nitrol-arginine methyl ester, cardiac energetics was measured by 31P nuclear magnetic resonance (NMR) spectroscopy and substrate oxidation profile was assessed by 13C-isotopmer analysis. Mitochondrial functions were assessed in the heart tissue and human induced pluripotent stem cell–derived cardiomyocytes. RESULTS: HFpEF hearts presented a lower phosphocreatine content and a reduced phosphocreatine/ATP ratio, similar to that in heart failure with reduced ejection fraction. Decreased respiratory function and increased reactive oxygen species production were observed in mitochondria isolated from HFpEF hearts suggesting mitochondrial dysfunction. Cardiac substrate oxidation profile showed
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Yoshii et al found that enhancing #FAO in the heart stimulated #mitophagy & improved #HFpEF phenotypes. Find out more about mitochondrial quality control & pathogenesis of HFpEF at https://t.co/mjJXW9bJtK @TianLab @durbaluckily https://t.co/XvLhcHI8gE
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Mashup Score: 5Discover CircRes November 2024 | AHA Podcasts - 1 day(s) ago
Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast of the American Heart Association’s journal, Circulation Research. I’m your host, Dr. Cynthia St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today, I’ll be highlighting articles from our October 25th and November 8th issues of Circulation Research. I’m also going to have a chat with Dr. Jil Tardiff and Dr. Melissa Lynn about their study, Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
1/5 New @CircRes podcast #DiscoverCircRes https://t.co/BjKCvjArjS @StHilaireLab chats with @jct_ucb & Melissa Lynn about their study Arg92Leu- cardiac troponin T Alters the cardiac troponin C-cardiac troponin I Interface Disrupting PKA-Mediated Relaxation https://t.co/8PXklZDZPe https://t.co/QP9XYgLs7d
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Mashup Score: 4Visualizing Immune Checkpoint Inhibitors Derived Inflammation in Atherosclerosis | Circulation Research - 1 day(s) ago
BACKGROUND: Immune checkpoint inhibitor (ICI) usage has resulted in immune-related adverse events in patients with cancer, such as accelerated atherosclerosis. Of immune cells involved in atherosclerosis, the role of CCR2+ (CC motif chemokine receptor 2-positive) proinflammatory macrophages is well documented. However, there is no noninvasive approach to determine the changes of these cells in vivo following ICI treatment and explore the underlying mechanisms of immune-related adverse events. Herein, we aim to use a CCR2 (CC motif chemokine receptor 2)–targeted radiotracer and positron emission tomography (PET) to assess the aggravated inflammatory response caused by ICI treatment in mouse atherosclerosis models and explore the mechanism of immune-related adverse events. METHODS: Apoe−/− mice and Ldlr−/− mice were treated with an ICI, anti-PD1 (programmed cell death protein 1) antibody, and compared with those injected with either isotype control IgG or saline. The radiotracer 64Cu-DOT
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Lou & colleagues report a non-invasive approach to visualize the adverse effects of #ICIs on the #cardiovascular system to uncover the mechanism for development of novel treatment. Learn more at https://t.co/ehO9UcHdIE @yongjianliu3 @junedh_amrute @XiulZhang https://t.co/ATs1I2pDSZ
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Mashup Score: 3LRP1 Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases | Circulation Research - 1 day(s) ago
BACKGROUND: Genome-wide association studies implicate common genetic variations in the LRP1 (low-density lipoprotein receptor-related protein 1 gene) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. METHODS: Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells were genome-edited using CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein 9) to delete or modify candidate enhancer regions and generate LRP1 knockout cell lines. Cells were differentiated into smooth muscle cells through a mesodermal lineage. Transcription regulation was assessed using luciferase reporter assay, transcription factor knockdown, and chromatin immunoprecipitation. Phenotype changes in cells were conducted using cellular assays, bulk RNA sequencing, and mass spectrometry. RESULTS: Multitrait colocalization analyses pointe
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Liu et al describe molecular regulatory mechanisms involving #SNAIL & resulting in #ECM remodeling in #iPSC derived #SMCs at #LRP1 pleiotropic GWAS locus 4 vascular diseases. Find out more at https://t.co/dhFDYW7P6K @n_bouatianaji @cjouve https://t.co/7FIaJ4dSwQ
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Mashup Score: 4Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP | Circulation Research - 3 day(s) ago
BACKGROUND: Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear. METHODS: The embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2 flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre [Cyclization recombinase] recombinase) under the α-myosin heavy chain promoter. RESULTS: Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurr
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Kang et al found that cardiomyocyte deletion of #Lphn2 a marker of cardiac #progenitors during differentiation of #PSC, induces #DCM. Learn more at at https://t.co/zhkaydnJp0 @MOOKANG @snuh_official https://t.co/j1T25kVWvq
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Mashup Score: 0Author Hub | AHA/ASA Journals - 4 day(s) ago
Rigorous, dependable research has always been at the core of the American Heart Association (AHA) mission to be a relentless force for a world of longer, healthier lives and vision of advancing health and hope for everyone, everywhere. Offering 14 scientific research journals that cover the breadth of cardiovascular and cerebrovascular disease, the AHA serves the specific needs of investigators and clinicians in subspecialties by providing online access to full-text articles for Professional, Early
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Connect with the #AHAJournals at our new Author Hub! #ESCCongress Go to https://t.co/Uaz0XAfF3H to explore today
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Mashup Score: 0Author Hub | AHA/ASA Journals - 4 day(s) ago
Rigorous, dependable research has always been at the core of the American Heart Association (AHA) mission to be a relentless force for a world of longer, healthier lives and vision of advancing health and hope for everyone, everywhere. Offering 14 scientific research journals that cover the breadth of cardiovascular and cerebrovascular disease, the AHA serves the specific needs of investigators and clinicians in subspecialties by providing online access to full-text articles for Professional, Early
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Connect with the #AHAJournals at our new Author Hub! #ESCCongress Go to https://t.co/Uaz0XAfF3H to explore today
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Mashup Score: 0Author Hub | AHA/ASA Journals - 5 day(s) ago
Rigorous, dependable research has always been at the core of the American Heart Association (AHA) mission to be a relentless force for a world of longer, healthier lives and vision of advancing health and hope for everyone, everywhere. Offering 14 scientific research journals that cover the breadth of cardiovascular and cerebrovascular disease, the AHA serves the specific needs of investigators and clinicians in subspecialties by providing online access to full-text articles for Professional, Early
Source: www.ahajournals.orgCategories: General Medicine News, CardiologistsTweet-
Connect with the #AHAJournals at our new Author Hub! #ESCCongress Go to https://t.co/Uaz0XAfF3H to explore today
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Chen et al found #EPHB4 receptor tyrosine kinase & #RASA1 interact physically in lymphatic #ECs to regulate the development of #lymphatic #vessel valves. Learn more about the mechanism of lymphatic vessel valve development at https://t.co/Jk39d70Jxs @UMMicroImmuno https://t.co/suvLb9C2kZ