Discover CircRes

This month on Episode 60 of Discover CircRes, host Cindy St. Hilaire highlights original research articles featured in the May 10 and May 24th issues of Circulation Research. This Episode also includes a discussion with Dr Sophie Astrof and Dr AnnJosette Ramirez from Rutgers University about their study, Buffering Mechanism in Aortic Arch Artery Formation and Congenital Heart Disease. Article highlights: Tamiato, et al. Pericyte RGS5 in Cardiac Aging Zifkos, et al. PTP1B and Venous Thromboinflammation Ma, et al. NR4A3 in Vascular Calcification Sultan, et al. VEGF-B Induced Coronary Endothelial Cell Lineage

This month on Episode 59 of Discover CircRes, host Cindy St. Hilaire highlights original research articles featured in the April 12 and April 26 issues of Circulation Research. This Episode also includes a discussion with Dr Craig Morrell and Chen Li from University of Rochester about their study, Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function. Article highlights: Arkelius, et al. LOX-1 and MMP-9 Inhibition Improves Stroke Outcomes Cruz, et al. C122Y Disrupts Kir2.1-PIP2 Interaction in ATS1 Blaustein, et al. Environmental Impacts on Cardiovascular Health and Biology: An Overview

This month on Episode 58 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the March 1 and March 15th issues of Circulation Research. This Episode also includes a discussion with Drs Frank Faraci, Tami Martino, and Martin Young about their contributions to the Compendium on Circadian Mechanisms in Cardiovascular and Cerebrovascular Disease. Article highlights: Yan, et al. GCN2 in Ponatinib-Induced Cardiotoxicity Wang, et al. Activating v-ATPase Ameliorates Cardiac Cardiomyopathy

This month on Episode 57 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the February 2nd and February 19 issues of Circulation Research. This Episode also includes a discussion with Dr Kathryn Howe and Dr Sneha Raju from University of Toronto, about their manuscript titled Directional Endothelial Communication by Polarized Extracellular Vesicle Release. Article highlights: Ren, et al. ZBTB20 Regulates Cardiac Contractility Faleeva, et al. Sox9 Regulates Vascular Extracellular Matrix Aging Bai, et al. PKA Is Critical for Cardiac Growth Wang, et al. Indole-3-Propionic Acid Protects Against HFpEF

This month on Episode 56 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the January 5 and January 19 issues of Circulation Research. This Episode also includes a discussion with Dr Julie Freed and Gopika Senthilkumar from the Medical College of Wisconsin about their study, Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease. Article highlights: He, et al. T Cell LGMN Deficiency Prevents Hypertension Salyer, et al. TnI-Y26 Phosphorylation Improves Relaxation Jacob, et al. MFN2 in Megakaryocyte and Platelet Function

This month on Episode 55 of Discover CircRes, host Cynthia St. Hilaireaire highlights two original research articles featured in the December 8th issue of Circulation Research. This Episode also includes a discussion with Dr José Luis de la Pompa and Dr Luis Luna-Zurita from the National Center for Cardiovascular Research in Spain about their study, Cooperative Response to Endocardial NOTCH Reveals Interaction With Hippo Pathway. Article highlights: Shi, et al. Nat10 Mediated ac4C in Cardiac Remodeling Knight, et al. CDK4 Oxidation Attenuates Cell Proliferation

This month on Episode 54 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the October 27th and November 10th issues of Circulation Research. This Episode also includes a discussion with Dr Sophie Susen and Dr Caterina Casari about their study, Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia, published in the October 27th issue. Article highlights: Pass, et al. Single Nuclei Transcriptome of PAD Muscle Liu, et al. Myocardial Recovery in DCM: CDCP1 and Fibrosis Grego-Bessa, et al. Neuregulin-1 Regulates Chamber Morphogenesis Agrawal, et al. A New Model of PH due to HFpEF

This month on Episode 53 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the September 29 and October 13th issues of Circulation Research. This Episode also includes a discussion with Dr Margaret Schwarz and Dr Dushani Ranasinghe about their study, Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension, published in the September 29 issue. Article highlights: Serio, et al. p300/CBP-Upregulated Glycolysis and Cardiac Aging Sharifi, et al. ADAMTS-7 and TIMP-1 in Atherosclerosis Zhang, et al. TMEM215 Represses Endothelial Apoptosis Perike, et al. PPP1R12C Promotes Atrial Hypocontractility in AF

This month on Episode 52 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the September 1 and September 15th issues of Circulation Research. This Episode also includes a discussion with Dr Manuel Mayr about the study, Proteomic Atlas of Atherosclerosis, the Contribution of Proteoglycans to Sex Differences, Plaque Phenotypes and Outcomes, published in the September 15 issue. Article highlights: Sun, et al. CCND2 modRNA Remuscularization Hearts with AMI Ho, et al. Lymphatic Genes Prevent Cardiac Valve Disease Shanks, et al. Cardiac Vagal Activity Increases During Exercise

This month on Episode 51 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the August 4 and August 18 issues of Circulation Research. This Episode also includes a discussion with Dr Eric Small and Dr Xiaoyi Liu from the University of Rochester Medical Center about their article p53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricular Pressure Overload, published in the July 21 issue of the journal. Article highlights: Régnier, et al. CTLA-4 Pathway Is Pivotal in Giant Cell Arteritis Zarkada, et al. Chylomicrons Regulate Lacteal Permeability Schuermans, et al. Age at Menopause, Telomere Length, and CAD Bayer, et al. T-cell MyD88 Regulates Fibrosis in Heart Failure

This month on Episode 50 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the June 23, July 7, and July 21 issues of Circulation Research. This Episode also includes a discussion with BCVS Outstanding Early Career Investigator Award Qiongxin Wang from University of Washington St. Louis, Haobo Li from Massachusetts General Hospital, and Asma Boukhalfa from Tufts Medical Center. Article highlights: Tong, et al. The Role of DRP1 in Mitophagy Abe, et al. ERK5-NRF2 Axis and Senescence-Associated Stemness Dai, et al. Therapeutic Targeting of Endocytosis Defects in DCM Weng, et al. PDCD5 Suppresses Cardiac Fibrosis

This month on Episode 49 of Discover CircRes, host Cynthia St. Hilaire highlights two original research articles featured in the May 26 issue and provides an overview of the June 9th Compendium on Early Cardiovascular Disease of Circulation Research. This Episode also includes a discussion with Dr Tejasvi Dudiki and Dr Tatiana Byzova about their study, Mechanism of Tumor Platelet Communications in Cancer. Article highlights: Nichtová, et al. Mitochondria-SR Tethering and Cardiac Remodeling Ferrucci, et al. Muscle Transcriptomic and Proteomic in PAD Compendium on Early Cardiovascular Disease.

This month on Episode 48 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the April 28th issue of Circulation Research. This Episode also includes a discussion between Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova, who all contributed to manuscripts to the May 12 Compendium on Covid-19 and the Cardiovascular System. Article highlights: Heijman, et al. Mechanisms of Enhanced SK-Channel Current in AF Chen, et al. IL-37 Attenuates Platelet Activation Enzan, et al. ZBP1 Protects Against Myocardial Inflammation Compendium on Covid-19 and the Cardiovascular System. 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 Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today, I'm going to be highlighting articles from our April 28th and May 12th issues of Circulation Research. I'm also going to have a chat with Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova, who all contributed to articles in the May 12th COVID Compendium. But before we have that interview, let's first talk about some highlights. The first article I want to present is titled Enhanced Calcium-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation. This article is coming from the University of Essen by Heijman and Zhou, et al. Atrial fibrillation is one of the most common forms of heart arrhythmia in humans and is characterized by irregular, often rapid heartbeats that can cause palpitations, dizziness and extreme fatigue. Atrial fibrillation can increase a person's risk of heart failure, and though treatments exist such as beta blockers, blood thinners and antiarrhythmia medications, they can have limited efficacy and side effects. A new family of drugs in development are those blocking small-conductance calcium-activated potassium channels called SK channels, which exhibit increased activity in animal models of AF and suppression of which attenuates the arrhythmia. In humans however, the relationship between SK channels and atrial fibrillation is less clear, at least in terms of SK channel mRNA levels. Because mRNA might not reflect actual channel activity, this group looked at just that and they found indeed that channel activity was increased in cardiomyocytes from atrial fibrillation patients compared to those from controls even though the mRNA and protein levels themselves were similar. The altered currents were instead due to changes in SK channel trafficking and membrane targeting. By confirming that SK channels play a role in human atrial fibrillation, this work supports the pursuit of SK channel inhibitors as possible new atrial fibrillation treatments. The next article I want to present is titled IL-37 Attenuates Platelet Activation and Thrombosis Through IL-1R8 Pathway. This article comes from Fudan University by Chen and Hong, et al. Thrombus formation followed by the rupture of a coronary plaque is a major pathophysiological step in the development of a myocardial infarction. Understanding the endogenous antithrombotic factors at play could provide insights and opportunities for developing treatments. With this in mind, Chen and Hong, et al. investigated the role of interleukin-1 receptor 8, or IL-1R8, which suppresses platelet aggregation in mice, and of IL-37, a newly discovered human interleukin that forms a complex with IL-1R8 and is found at increased levels in the blood of patients with myocardial infarction. Indeed, the amount of IL-37 in myocardial infarction patients negatively correlates with platelet aggregation. They also show that treatment of human platelets in vitro with IL-37 suppresses the cell's aggregation and does so in a concentration-dependent manner. Moreover, injection of the protein into the veins of mice inhibits thrombus development and better preserves...

This month on Episode 47 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the March 31 issue of Circulation Research. We’ll also provide an overview of the Compendium on Increased Risk of Cardiovascular Complications in Chronic Kidney Disease published in the April 14 issue. Finally, this episode features an interview with Dr Elizabeth Tarling and Dr Bethan Clifford from UCLA regarding their study, RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels. Article highlights: Shi, et al. LncRNAs Regulate SMC Phenotypic Transition Chen, et al. Bilirubin Stabilizes Atherosclerotic Plaque Subramaniam, et al. Mapping Non-Obvious cAMP Nanodomains by Proteomics Compendium on Increased Risk of Cardiovascular Complications in Chronic Kidney Disease 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 Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to share three articles selected from our March 31st issue of Circulation Research and give you a quick summary of our April 14th Compendium. I'm also excited to speak with Dr Elizabeth Tarling and Dr Bethan Clifford from UCLA regarding their study, RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels. So first the highlights. The first article we're going to discuss is Discovery of Transacting Long Noncoding RNAs that Regulates Smooth Muscle Cell Phenotype. This article's coming from Stanford University and the laboratory of Dr Thomas Quertermous. Smooth muscle cells are the major cell type contributing to atherosclerotic plaques. And in plaque pathogenesis, the cells can undergo a phenotypic transition whereby a contractile smooth muscle cell can trans differentiate into other cell types found within the plaque, such as macrophage-like cells, osteoblast-like cells and fibroblast-like cells. These transitions are regulated by a network of genetic and epigenetic mechanisms, and these mechanisms govern the risk of disease. The involvement of long non-coding RNAs, or Lnc RNAs as they're called, has been increasingly identified in cardiovascular disease. However, smooth muscle cell Lnc RNAs have not been comprehensively characterized and the regulatory role in the smooth muscle cell state transition is not thoroughly understood. To address this gap, Shi and colleagues created a discovery pipeline and applied it to deeply strand-specific RNA sequencing from human coronary artery smooth muscle cells that were stressed with different disease related stimuli. Subsequently, the functional relevancy of a few novel Lnc RNAs was verified in vitro. From this pipeline, they identified over 4,500 known and over 13,000 unknown or previously unknown Lnc RNAs in human coronary artery smooth muscle cells. The genomic location of these long noncoding RNAs was enriched near coronary artery disease related transcription factor and genetic loci. They were also found to be gene regulators of smooth muscle cell identity. Two novel Lnc RNAs, ZEB-interacting suppressor or ZIPPOR and TNS1-antisense or TNS1-AS2, were identified by the screen, and this group discovered that the coronary artery disease gene, ZEB2, which is a transcription factor in the TGF beta signaling pathway, is a target for these Lnc RNAs. These data suggest a critical role for long noncoding RNAs in smooth muscle cell phenotypic transition and in human atherosclerotic disease. Cindy St. Hilaire: The second article I want to share is titled Destabilization of Atherosclerotic Plaque by Bilirubin Deficiency. This article is coming from the Heart Research Institute and the corresponding author is Roland Stocker. The rupture of atherosclerotic plaque contributes significantly to cardiovascular disease. Plasma concentrations of bilirubin, a byproduct of heme catabolism, is inversely...

This month on Episode 46 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the March 3 and March 17th issues of Circulation Research. This episode also features an interview with Dr Andrew Hughes and Dr Jessilyn Dunn about their review, Wearable Devices in Cardiovascular Medicine. Article highlights: Delgobo, et al. Deep Phenotyping Heart-Specific Tregs Sun, et al. Inhibition of Fap Promotes Cardiac Repair After MI Sun, et al. Endosomal PI3Kγ Regulates Hypoxia Sensing Johnson, et al. Hypoxemia Induces Minimal Cardiomyocyte Division 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 Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today I'm going to share four articles selected from the March 3rd and March 17th issues of CircRes. I'm also going to have a discussion with Dr Andrew Hughes and Dr Jessilyn Dunn about their review, Wearable Devices in Cardiovascular Medicine. And the Review is also featured in our March 3rd issue. Cindy St. Hilaire: First, the highlights. The first article I'm going to present is Myocardial Milieu Favors Local Differentiation of Regulatory T-Cells. The first author is Murilo Delgobo and the corresponding author is Gustavo Campos Ramos. After myocardial infarction, the release of autoantigens from the damaged heart cells activates local and infiltrating immune cells such as the T-cell. Studies in mice have shown that fragments of the muscle protein myosin can act as autoantigens, and these myosin fragments are the dominant driver of the T-cell response. But how do these myosin specific T-cells behave in the damaged heart to drive inflammation and repair is unknown. To find out, Delgobo and colleagues studied endogenous myosin specific T-cells, as well as those transferred into recipient mice. They found, whether exogenously supplied or endogenously created, the myosin specific T-cells that accumulated in the animals' infarcted hearts tended to adopt an immunosuppressive T-regulatory phenotype. Strikingly, even if the exogenous cells were differentiated into inflammatory TH-17 cells prior to transfer, a significant proportion of them were still reprogrammed into T-regs within the heart. Although cells pre-differentiated into an inflammatory TH-17 phenotype were less inclined to change after the transfer, the results nevertheless indicate that, by and large, the infarcted heart promotes T-cell reprogramming to quell inflammation and drive repair. Yet exactly how the heart does this is a question for future studies. Cindy St. Hilaire: The next article I'm going to present is titled Inhibition of FAP Promotes Cardiac Repair by Stabilizing BNP. The first authors of the study are Yuxi Sun and Mengqiu Ma, and the corresponding author is Rui Yue, and they are from Tongji University. After myocardial infarction, there needs to be a balance of recovery processes to protect the tissue. Fibrosis, for example, acts like an immediate bandaid to hold the damaged heart muscle together, but fibrosis can limit contractile function. Similarly, angiogenesis and sufficient revascularization is required to promote survival of cardiomyocytes within the ischemic tissue and protect heart function. To better understand the balance between fibrotic and angiogenic responses, Sun and colleagues examined the role of fibroblasts activated protein, or FAP, which is dramatically upregulated in damaged hearts, and brain natriuretic peptide, or BNP, which promotes angiogenesis in the heart. In this study, they found that genetic deletion or pharmacological inhibition of FAP in mice reduces cardiac fibrosis and improves angiogenesis and heart function after MI. Such benefits are not seen if BNP or its receptor, NRP-1, are lacking. The in vitro experiments revealed that FAP's protease...

This month on Episode 45 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the February 3rd and February 17th issues of Circulation Research. This episode also features an interview with Dr Hind Lal and Dr Tousif Sultan from the University of Alabama at Birmingham about their study Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. Article highlights: Pi, et al. Metabolomic Signatures in PAH Carnevale, et al. Thrombosis TLR4-Mediated in SARS-CoV-2 Infection Cai, et al. Macrophage ADAR1 in AAA Koide, et al. sEVs Accelerate Vascular Calcification in CKD 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'm going to be highlighting the articles from our February 3rd and 17th issues of Circulation Research. I'm also going to have a chat with Dr Hind Lal and Dr Tousif Sultan from the University of Alabama at Birmingham about their study, Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. But before I get to the interviews, here are a few article highlights. Cindy St. Hilaire: The first article I want to highlight comes from the laboratory of Dr Peter Leary at the University of Washington, and the title is Metabolomic Signatures Associated With Pulmonary Arterial Hypertension Outcomes. Pulmonary Arterial Hypertension or PAH is a rare but life-threatening disease in which progressive thickening of the walls of the lung’s blood vessels causes increased blood pressure and that increased blood pressure ultimately damages the heart's right ventricle. Interestingly, progression to heart failure varies considerably among patients, but the reasons why there is variability are not well understood. To find out, this group turned their attention to patient metabolomes, which differ significantly from those of healthy people and thus may also change with severity. Blood samples from 117 PAH patients were analyzed for more than a thousand metabolites by mass spectrometry and the patient's progress was followed for the next three years. 22 patients died within a three-year period and 27 developed significant right ventricle dilation. Other measures of severity included pulmonary vascular resistance, exercise capacity and levels of BNP, which is a metric of heart health. Two metabolic pathways, those relating to polyamine and histidine metabolism, were found to be linked with all measures of severity suggesting a key role for them in disease pathology. While determining how these pathways influence disease as a subject for further study, the current findings may nevertheless lead to new prognostic indicators to inform patient care. Cindy St. Hilaire: The next article I want to discuss is coming from our February 3rd issue of Circulation Research and this is coming from the laboratory of Dr Francisco Violi at the University of Rome and the title is Toll-Like Receptor 4-Dependent Platelet-Related Thrombosis in SARS-CoV-2 Infection. Thrombosis can be a complication of COVID-19 and it is associated with poor outcomes, including death. However, the exact mechanism by which the virus activates platelets, which are the cells that drive thrombosis, is not clear. For one thing, platelets do not appear to express the receptor for SARS-CoV-2. They do however, express the TLR4 receptor and that's a receptor that mediates entry of other viruses as part of the immune response. And TLR4 is ramped up in COVID-19 patient platelets. This group now confirms that, indeed, SARS-CoV-2 interacts with TLR4, which in turn triggers thrombosis. The team analyzed platelets from 25 patients and 10 healthy controls and they found that the platelet activation and thrombic activity were both boosted in the patient samples...

This month on Episode 44 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the January 6 and January 20th issue of Circulation Research. This episode also features an interview with Dr Timothy McKinsey and Dr Marcello Rubino about their study, Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart. Article highlights: Prasad, et al. ACE2 in Gut Integrity and Diabetic Retinopathy Cui, et al. Epsins Regulate Lipid Metabolism and Transport Li, et al. Endothelial H2S modulates EndoMT in HF Luo, et al. F. plautii Attenuates Arterial Stiffness 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 Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh. And today I'm going to be highlighting articles from our January 6th and January 20th issues of Circulation Research. I'm also going to have a chat with Dr Timothy McKinsey and Dr Marcello Rubino about their study, Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart. But before the interview, I want to get to a few articles to highlight. Cindy St. Hilaire: The first article is titled, Maintenance of Enteral ACE2 Prevents Diabetic Retinopathy in Type 1 Diabetes. The first authors are Ram Prasad and Jason Floyd, and the corresponding author is Maria Grant, and they are from the University of Alabama. Type 1 Diabetes has a complex etiology and pathology that are not entirely understood. In addition to the destruction of insulin-producing cells, a recently discovered feature of the disease in both humans and in rodent models is that the levels of angiotensin converting enzyme 2 or ACE2 can be unusually low in certain tissues. ACE2 is a component of the renin angiotensin system controlling hemodynamics and interestingly, genetic deficiency of ACE2 in rodents exacerbates aspects of diabetes such as gut permeability, systemic inflammation and diabetic retinopathy, while boosting ACE2 has been shown to ameliorate diabetic retinopathy in mice. This study shows that ACE2 treatment also improves gut integrity and systemic inflammation as well as retinopathy. Six months after the onset of diabetes in a mouse model, oral doses of a bacteria engineered to express humanized ACE2 led to a reversal of the animal's gut barrier dysfunction and its retinopathy. Humans with diabetic retinopathy also displayed evidence of increased gut permeability in low levels of ACE2. This study suggests they may benefit from a similar probiotic treatment. Cindy St. Hilaire: The next article I want to highlight is titled, Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression. The first authors are Kui Cui, Xinlei Gao and Beibei Wang, and the corresponding authors are Hong Chen and Kaifu Chen and they're from Boston Children's Hospital. Epsins are a family of plasma membrane proteins that drive endocytosis. They're expressed at varying levels throughout the tissues of the body, and recent research shows that they are unusually abundant on macrophages within atherosclerotic lesions. In mice, macrophage specific Epsin loss results in a reduction in foam cell formation and atherosclerotic plaque development. This study now shows that this effect on foam cells is because Epsins normally promote the internalization of lipids into macrophages through their endosytic activity. But that's not all. The proteins also impede cholesterol efflux from macrophages to further exacerbate lipid retention. It turns out out Epsins regulate the endocytosis and the degradation of a cholesterol efflux factor called ABCG1. Importantly, these pro atrogenic activities of Epsins can be stopped. Using macrophage targeted nanoparticles carrying Epson specific silencing RNA, the team could suppress reduction of the protein in cultured macrophages and could reduce the size and number...

This month on Episode 43 of Discover CircRes, guest host Nicole Purcell highlights two original research articles featured in the December 2 issue of Circulation Research. This episode also features an interview with Drs Aaron Phillips and Kevin O'Gallagher about their study, The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans. Article highlights: Akerberg, et al. RBPMS2 Regulates RNA Splicing in Cardiomyocytes Lv, et al. Cardiac Protection by MG53-S255A Mutant Nicole Purcell: Hi and welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I am your host, Dr Nicole Purcell, from the Huntington Medical Research Institutes in Pasadena, California, and today I will be highlighting two articles from our December 2 issue of Circulation Research. I'll also have a chat with Drs Aaron Phillips and Kevin O'Gallagher about their study, The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans. Nicole Purcell: But before I get to the interview, here are a few article highlights. The first article we're going to highlight is RBPMS2 Is a Myocardial Enriched Splicing Regulator Required for Cardiac Function. This comes from Boston Children's Hospital with first author Dr Alexander Akerberg, and corresponding author Dr Jeffrey Burns. RNA splicing, along with transcription control and post-translational modifications, is a mechanism for fine tuning the expression of a gene for a particular purpose in a particular tissue. Factors that control splicing are thus often enriched in certain cell types. The factor, RBPMS2, for example, is enriched in the myocytes of amphibians, fish, birds and mammals. This conserve tissue specificity suggesting essential role of RBPMS2 in heart function. Akerberg and colleagues now confirm this is indeed the case. They generated zebra fish embryos and human cardiomyocytes lacking RBPMS2, and found the fish suffered early cardiac dysfunction by 48 hours post fertilization. The animal's hearts had reduced ejection fractions, compared with the hearts of controlled fish. At the cellular level, the RBPMS2 lacking fish cardiomyocytes displayed malformed sarcomere fibers and disrupted calcium handling, both of which were also seen in the RBPMS2 deficient human cardiomyocytes. Furthermore, RNA sequencing experiments revealed a conserve set of 29 genes in the RBPMS2-lacking fish and human cells that were incorrectly spliced. In revealing the essential cardiac role of RBPMS2 and its RNA targets, the work provides new molecular details for understanding vertebrate heart function and disease, say the team. Nicole Purcell: Our second article being highlighted is Blocking MG53 Serine 255 Phosphorylation Protects Diabetic Heart from Ischemic Injury. This comes from Peking University with first authors, Fengxiang L, Yingfan Wang and Dan Shan, as well as corresponding author Dr Rui-Ping Xiao. Midsegment 53, or MG53, is a recently discovered muscle-specific protein that is an essential component of the cell membrane repair machinery with cardioprotective effects. MG53 thus has therapeutic potential, but for patients whose heart disease is linked to type 2 diabetes, there's a problem. MG53 also tags certain cellular proteins for destruction, including the insulin receptor and the insulin signaling factor, IRS1. Loss of these factors could worsen insulin resistance. lev and colleagues therefore investigate whether MG53 could be tweaked to provide protection without the diabetes downside. Nicole Purcell: They discovered the phosphorylation of MG53 at serine 255 is required for its role in protein destruction, and that a mutant version of MG53, incapable of this phosphorylation, MG53 serine to 255 alanine mutant, could still promote cardiomyocyte survival, and protect the cells from membrane damaging insults. Importantly, when a diabetic mouse model was injected with MG53 serine...

This month on Episode 42 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the October 28 and November 11 issues of Circulation Research. This episode also features an interview with Dr Miguel Lopez-Ramirez and undergraduate student Bliss Nelson from University of California San Diego about their study, Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformations. Article highlights: Jia, et al. Prohibitin2 Maintains VSMC Contractile Phenotype Rammah, et al. PPARg and Non-Canonical NOTCH Signaling in the OFT Wang, et al. Histone Lactylation in Myocardial Infarction Katsuki, et al. PCSK9 Promotes Vein Graft Lesion Development 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 Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today, I'm going to be highlighting articles from our October 28th and our November 11th issues of Circ Res. I'm also going to have a chat with Dr Miguel Lopez-Ramirez and undergraduate student Bliss Nelson, about their study, Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformations. But, before I get into the interviews, here are a few article highlights. Cindy St. Hilaire: The first article is from our October 28th issue, and the title is, PHB2 Maintains the Contractile Phenotype of Smooth Muscle Cells by Counteracting PKM Splicing. The corresponding author is Wei Kong, and the first authors are Yiting Jia and Chengfeng Mao, and they are all from Peking University. Insults to blood vessels, whether in the form of atherosclerosis, physical injury, or inflammation, can trigger vascular smooth muscle cells to transition from a contractile state to a proliferative and migratory one. Accompanying this conversion is a switch in the cells' metabolism from the mitochondria to glycolysis. But what controls this switch? To investigate, this group compared the transcriptomes of contractile and proliferative smooth muscle cells. Among the differentially expressed genes, more than 1800 were reciprocally up and down regulated. Of those, six were associated with glucose metabolism, including one called Prohibitin-2, or PHB2, which the team showed localized to the artery wall. In cultured smooth muscle cells, suppression of PHB2 reduced expression of several contractile genes. While in rat arteries, injury caused a decrease in production of PHB2 itself, and of contractile markers. Furthermore, expression of PHB2 in proliferative smooth muscle cells could revert these cells to a contractile phenotype. Further experiments revealed PHB2 controlled the splicing of the metabolic enzyme to up-regulate the phenotypic switch. Regardless of mechanism, the results suggest that boosting PHB2 might be a way to reduce adverse smooth muscle cell overgrowth and conditions such as atherosclerosis and restenosis. Cindy St. Hilaire: The second article I'm going to highlight is also from our October 28th issue, and the first authors are Mayassa Rammah and Magali Theveniau-Ruissy. And the corresponding authors are Francesca Rochais and Robert Kelly. And they are all from Marseille University. Abnormal development of the heart's outflow track, which ultimately forms the bases of the aorta and the pulmonary artery, accounts for more than 30% of all human congenital heart defects. To gain a better understanding of outflow tract development, and thus the origins of such defects, this group investigated the role of transcription factors thought to be involved in specifying the superior outflow tract, or SOFT, which gives rise to the subaortic myocardium, and the inferior outflow tract, which gives rise to the subpulmonary myocardium. Transcription factor S1 is over-expressed in superior outflow tract cells and the transcription factors, TBX1 and PPAR gamma, are expressed in inferior...

This month on Episode 41 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the September 30 and October 14 issues of Circulation Research. This episode also features an interview with Dr Kory Lavine and Dr Chieh-Yu Lin from Washington University St. Louis, to discuss their study, Transcriptional and Immune Landscape of Cardiac Sarcoidosis. Article highlights: Tian, et al. EV-Mediated Heart Brain Communication in CHF Wleklinski, et al. Impaired Dynamic SR Ca Buffering Causes AD-CPVT2 Masson, et al. Orai1 Inhibition as a Treatment for PAH Li, et al. F. Prausnitzii Ameliorates Chronic Kidney Disease Cindy St. Hilaire: Hi, and welcome to Discover Circ Res, 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'm going to highlight articles from our September 30th and October 14th issues of Circulation Research. I'm also going to have a chat with Dr Kory Lavine and Dr Chieh-Yu Lin from Washington University St. Louis, and we're going to discuss their study Transcriptional and Immune Landscape of Cardiac Sarcoidosis. But before I get to the interview, I'm going to highlight a few articles. Cindy St. Hilaire: The first article I'm going to share is Extracellular Vesicles Regulate Sympathoexcitation by Nrf2 in Heart Failure. The first author of this study is Changhai Tian, and the corresponding author is Irving Zucker, and they are at University of Nebraska. After a myocardial infarction, increased oxidative stress in the heart can contribute to adverse cardiac remodeling, and ultimately, heart failure. Nrf2 is a master activator of antioxidant genes, suggesting a protective role, but studies in rats have shown its expression to be suppressed after MI, likely due to upregulation of Nrf2-targeting microRNAs. These microRNAs can also be packaged into vesicles and released from stressed heart cells. Now, this group has shown that rats and humans with chronic heart failure have an abundance of these microRNA-containing EVs in their blood. In the rats with chronic heart failure, these extracellular vesicles were found to be taken up by neurons of the rostral ventrolateral medulla, RVLM, wherein the microRNA suppressed Nrf2 expression. The RVLM is a brain region that controls the sympathetic nervous system, and in the presence of EVs, it is ramped up by sympathetic excitation. Because such elevated sympathetic activity can induce the fight or flight response, including increased heart rate and blood pressure, this would likely worsen heart failure progression. The team, however, found that inhibiting microRNAs in the extracellular vesicles prevented Nrf2 suppression in the RVLM and sympathetic activation, suggesting the pathway could be targeted therapeutically. Cindy St. Hilaire: The next article I want to highlight is titled, Impaired Dynamic Sarcoplasmic Reticulum Calcium Buffering in Autosomal Dominant CPVT2. The first author of this study is Matthew Wleklinski, and the corresponding author is Bjӧrn Knollmann, and they are at Vanderbilt University. Exercise or emotional stress can prompt the release of catecholamine hormones, which induce a fast heart rate, increased blood pressure, and other features of the fight or flight response. For people with catecholaminergic polymorphic ventricular tachycardia, or CPVT, physical activity or stress can cause potentially lethal arrhythmias. Mutations of calsequestrin-2, or CASQ2, which is a sarcoplasmic reticulum calcium-binding protein, is a major cause of CPVT, and can be recessive or dominant in nature. For many recessive mutations, disease occurs due to loss of CASQ2 protein. This group investigated a dominant lysine to arginine mutation in this protein, and found by contrast, protein levels remain normal. In mice carrying the mutation, not only was the level of...