8 episódios

Each 15-minute podcast will provide an overview of the issue’s contents and relevant news in the field of basic/translational cardiovascular biology followed by an in-depth discussion of a featured article. This discussion will pull opinions from the podcast hosts, editorial team, research leaders and authors – both the corresponding authors as well as the trainee(s). We will provide lively discussions that give the listener a behind the scenes look at how science gets done and the implications of these fascinating discoveries.

Discover CircRes Cynthia St. Hilaire, PhD & Milka Koupenova, PhD

    • Ciências da vida

Each 15-minute podcast will provide an overview of the issue’s contents and relevant news in the field of basic/translational cardiovascular biology followed by an in-depth discussion of a featured article. This discussion will pull opinions from the podcast hosts, editorial team, research leaders and authors – both the corresponding authors as well as the trainee(s). We will provide lively discussions that give the listener a behind the scenes look at how science gets done and the implications of these fascinating discoveries.

    January 2020 Discover CircRes

    January 2020 Discover CircRes

    This month on Episode 8 of the Discover CircRes podcast, host Cindy St. Hilaire  speaks with Nikki Purcell and  Sean Wu, the chair and vice-chair of the BCVS Early Career Committee. The episode also features an interview with the 2019 BCVS Early Career Finalists, Dr Luigi Adamo, Dr Swati Dey, and Dr Jihoon Nah. In addition, we highlight three featured articles from the January 3 and January 17, 2020 issues of Circulation Research.
     
    Article highlights:

     
    Souza, et al. Upregulation of Plasma SPM by Enriched Marine Oils
     
    Paredes, et al. Metabolic Control of VSMC Phenotype
     
    Ritterhoff, et al.  ACC2 Deletion Prevents Aspartate Synthesis
    Transcript

    Dr St. Hilaire: Hi. Welcome to Discover CircRes, the podcast of the American Heart Association Journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, and I'm an assistant professor at the University of Pittsburgh.
    The goal of this podcast is to share with you highlights from recent articles published in the Circulation Research Journal. But today, we're going to have a special edition focused on early career.
    The American Heart Association has 16 different councils. One of which is basic cardiovascular sciences,  or BCVS. The BCVS Scientific Sessions is held annually and brings together basic and translational cardiovascular scientists from around the world. It has become the go-to meeting for intra and interdisciplinary cross fertilization of ideas in basic cardiovascular research.
    The overarching goal is to integrate molecular, and cellular, and physiological approaches to address problems relating to functional genomics, cell signaling, myocardial biology, circulatory physiology, pathophysiology, and peripheral vascular disease.
    In addition to highlighting new approaches and discoveries from the general scientific community, the BCVS Council also plays a pivotal role in training the next generation of junior scientists and trainees. At the recent meeting in Boston, I had the opportunity to interview the chair and vice chair of the BCVS Early Career Committee, Dr Nicole Purcell from UCSD, and Dr Sean Wu from Stanford University, as well as the three finalists of the Outstanding Early Career Investigator Award competition, Dr Luigi Adamo, Dr Swati Dey, and Jihoon Nah. Hope you enjoy.
    Before we get to our interviews with the BCVS early career committee chairs, and the finalists of the BCVS Outstanding Early Career Investigator Award, I want to give you a few highlights from three articles that were published in the January 3rd and January 17th issues of Circulation Research. The first article I'd like to highlight is titled Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study. The first authors are Patricia Souza and Raquel Marques, and the corresponding author is Jesmond Dalli, and they are from Queens Mary University of London.
    So, this study is attempting to answer the longstanding question of whether I should or should not take fish oil supplements. Once ingested into the body, essential fatty acids, which is a group that includes those that are found in fish oils--those fatty acids are converted into molecules called specialized pro resolving mediators, or SPMs. SPMs can reduce inflammation and can also promote a process called phagocytosis where immune cells can essentially eat up dead cell debris and also micro-organisms like bacteria.
    While these actions are beneficial, whether ingesting fish oils translates to beneficial cardiovascular effects in humans, is unclear. Some studies show the oils reduce inflammation, while others have shown no effect. And part of the lack of clarity on this is that in previous studies there was no impartial measure of the clinical efficacy of the supplements. So

    • 34 min
    December 2019 Discover CircRes

    December 2019 Discover CircRes

    This month on Episode 7 of the Discover CircRes podcast, host Cindy St. Hilaire highlights two featured articles from the December 6, 2019 issue of Circulation Research and talks with Roy Silverstein and Yiliang Chen about their article, Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses.
    Article highlights:

    McArdle, et al, et al. Migratory and Dancing Atherosclerotic Macrophages
    Skaria, et al. Cardioprotection with Endogenous αCGRP
    Transcript

    Dr Cindy St. Hilaire: Hi, welcome to Discover CircRes the monthly podcast of the American Heart Association journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, and I'm an Assistant Professor at the University of Pittsburgh. In this episode I'm going to share with you highlights from recent articles published in the December 6 issue of Circulation Research. We're also going to have an in-depth conversation with Drs Roy Silverstein and Yiliang Chen about their recent article on how macrophage CD36 modulates immunometabolism. Also, the American Heart Association Scientific Sessions were recently held in Philadelphia, PA and in this edition of Discover CircRes, we're going to feature a conversation with the editors in chief of Circulation Research and Circulation, Drs Jane Friedman and Joe Hill.
    The first article I'd like to highlight is titled Migratory Dancing Atherosclerotic Macrophages. The first author is Sarah McCardell and the corresponding author is Klaus Ley and the work was conducted at the La Jolla Institute of Immunology in La Jolla, California. A major component of atherosclerosis is the inflammatory response and atherosclerotic plaques contain a mix of macrophages. Some macrophages arise from proliferation of resident cells, while other macrophages can infiltrate in from the blood. And a few studies have shown that smooth muscle cells can acquire some macrophage-like markers. Some macrophages are anti-inflammatory while others are more pro-inflammatory. These variations have largely been determined using techniques that examine the cell surface marker expression, the transcription profiles, or by mass spectrometry. But how all these different types of macrophagia cells look and function in vivo has not been clearly defined nor visualized. McCardell and colleagues have now observed fluorescently-labeled macrophages in the atherosclerotic plaques of live mice.
    First, using single cell RNA sequencing, they identified key markers of macrophage subsets. These markers are Cx3cr1 and CD11c. They then generated Apoe knockout mice that could then express green fluorescent protein under the direction of the Cx3cr1 promoter and yellow fluorescent protein under the direction of CD11c. These fluorescent proteins could be expressed individually, they could be expressed together, or they could be expressed not at all. And then in these mice they used intravital microscopy to look at the carotid artery plaques and they found while green cells and double positive cells, so that is, cells expressing Cx3cr1or both Cx3cr1 and CD11c--these cells tended to stay in one place, but they could extrude these protrusions akin to dancing, while the yellow cells or the cells that were expressing CD11c alone were more spherical and migratory.
    RNA analysis revealed that migratory genes were indeed upregulated in the yellow cells as compared to the green cells. The work provides preliminary insights into plaque macrophage dynamics and presents a technical resource for investigating how such behaviors may influence disease progression and I highly recommend you check this article out online. They have included several videos in the supplementary data and they're really beautiful. You can actually see the macrophages moving around and dancing and moving through the tissue and it's really neat to think about maybe how people are going t

    • 29 min
    November 2019 Discover CircRes

    November 2019 Discover CircRes

    This month on Episode 6 of the Discover CircRes podcast, host Cindy St. Hilaire highlights five featured articles from the October 25 and November 8, 2019 issues of Circulation Research and talks with Coleen McNamara and Aditi Upadhye about their article, Diversification and CXCR4-Dependent Establishment of the Bone Marrow B-1a Cell Pool Governs Atheroprotective IgM Production Linked To Human Coronary Atherosclerosis.
     
    Article highlights:

     
    Omura, et al. ADAMTS8 in Pulmonary Hypertension.
     
    Rödel, et al. Blood Flow Suppresses CCM Phenotypes in Zebrafish
     
    Cai, et al. Proteomics Assessment of hPSC-CM Maturation
     
    Shin, et al. Leptin Causes Hypertension Via Carotid Body Trpm7
     
    Lin , et al. Cellular Heterogeneity in Elastin Deposition
     
    Transcript
    Dr Cindy St. Hilaire:          Hi. Welcome to Discover CircRes, the monthly podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire and I'm an assistant professor of medicine at the University of Pittsburgh. In this episode I'm going to share with you some highlights from recent articles that were published in the October 25th and our November 8th issues of Circulation Research.
    We're also going to have an in-depth conversation with doctors Coleen McNamara and Aditi Upadhye, who are the lead authors in one of the exciting discoveries from our October 25th issue.

    The first article I want to share with you is titled ADAMTS8 promotes the development of pulmonary arterial hypertension and right ventricular failure, a possible novel therapeutic target. The first author is Junichi Omura and the corresponding author is Hiroaki Shimokawa, and the work was conducted at Tohoku University, Sendai, Japan. Pulmonary hypertension is caused from the excessive proliferation of the vasculature in the lungs. It has contributions from smooth muscle cells, endothelial cells, inflammatory cells, and these cells proliferate and occlude the small vessels in the lungs. And this occlusion leads ultimately to failure of the right heart ventricle. Current therapies only treat the symptoms, not the underlying pathology. So there really is a big push right now to try to discover novel therapeutic targets.
    The authors of this study performed a gene expression screen, and in this screen, they compared pulmonary artery smooth muscle cells from pulmonary hypertension patients to those same cells from healthy controls. The research has found numerous differentially-expressed genes. However, they chose to focus on one called ADAMTS8. And they focused on this because the protein is expressed specifically in the lungs and heart tissues, and it was significantly upregulated in the patient's cells.
    So ADAMTS8 is a secreted zinc dependent protease, and this protease function makes it potentially a druggable target. So similar to human cells, ADAMTS8 was also found to be upregulated in the lungs of mice with pulmonary hypertension and a lack of vascular ADAMTS8 attenuated the disease symptoms. Conversely, overexpression of ADAMTS8 in pulmonary artery smooth muscle cells from both mice and humans prompted increased proliferation. They performed a high throughput screen to try and identify compounds that would suppress ADAMTS8 and pulmonary artery smooth muscle cell proliferation. And in this screen, they found mebendazole, which is a drug that is already in clinical use for parasitic worm infections. Thus, the study not only pins ADAMTS8 as a driver of pulmonary hypertension, but also suggests a potential existing drug might be useful for treating it.
    The next manuscript I want to share with you is titled Blood Flow Suppresses Vascular Anomalies In a Zebrafish Model of Cerebral Cavernous Malformations. The first author is Claudia Jasmin Rödel, and the corresponding author is Salim Abdelilah-Seyfried, and they are from the Unive

    • 27 min
    October 2019 Discover CircRes

    October 2019 Discover CircRes

    This month on Episode 5 of the Discover CircRes podcast, host Cindy St. Hilaire highlights five featured articles from the September 27 and October 11, 2019 issues of Circulation Research and talks with Sarvesh Chelvanambi and Matthias Clauss  about their article HIV-Nef Protein Transfer to Endothelial Cells Requires Rac1 Activation and Leads to Endothelial Dysfunction: Implications for Statin Treatment in HIV Patients.
     
    Article highlights:
     
    Stamatelopoulos, et al. Reactive Vasodilation in AL Amyloidosis
     
    Cao, et al. Miro2-Mediated Cardiac Mitochondrial Communication
     
    Georgakis, et al. Circulating MCP-1 Levels and Incident Stroke
     
    Sun, et al. Body Mass Index and DNA Methylation
     
    Tan, et al. Yy1 Suppresses DCM Through Bmp7 and Ctgf
    Transcript
    Cindy St. H:                       Hi. Welcome to Discover CircRes, the monthly podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you highlights from recent articles published in the September 27th and October 11th issues of Circulation Research.
                                               We'll also have an in-depth conversation with Drs Matthias Clauss and Sarvesh Chelvanambi, who are the lead authors in one of the exciting discoveries from our October 11th issue.
                                               The first article I want to share with you is titled, Reactive Vasodilation Predicts Mortality in Primary Systemic Light Chain Amyloidosis. The first authors are Drs Kimon Stamatelopoulos, Georgios Georgiopoulos, and the corresponding author is Dr Efstathios Kastritis. And the studies were conducted at the National Kapodistrian University of Athens School of Medicine in Athens, Greece.
                                               So we hear about amyloids a lot in things like Alzheimer's, but amyloids are really just aggregates of protein that fold into shapes. And the nature of these shapes allows these individual protein molecules to bind and form many copies that form these fibers that are rather sticky. And the fibers then aggregate into larger and larger globules. And light chain amyloidosis is the most common type of amyloidosis. It's a rare but deadly disease, and it's caused by antibody-producing cells that are aberrantly churning out parts of antibodies called light chains. And it's these light chains that will aggregate and form sticky fibers.
                                               So these fibers aggregate and form amyloid deposits, and these deposits build up and damage the organs and the tissue in which they're accumulating. And because it's dependent on where the aggregates are accumulating, AL amyloidosis can present with a wide variety of symptoms. However, symptoms of heart dysfunction and low blood pressure correlate with poor prognosis.
                                               And because vascular dysfunction can contribute to hypotension or low blood pressure, this group decided to examine the vascular health of patients by conducting a measurement called flow-mediated vasodilation. And so this is a measurement where the diameter of the brachial artery, which is located in your arm, is measured before and then after a brief period of lower arm ischemia. And they formed a cohort of 115 newly diagnosed AL patients and another cohort of 115 matched controls. This study found that in AL patients, flow-mediated vasodilation was higher than in aged, sex, and cardiovascular risk factor-matched controls. The mean follow-up time for

    • 29 min
    September 2019 Issue

    September 2019 Issue

    This month on the Discover CircRes podcast, host Cindy St. Hilaire highlights five featured articles from recent issues of Circulation Research and talks with Matthew Stratton, Rushita Bagchi, and Tim McKinsey about their article on Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation.
    Article highlights:
    Vincentz, et al. HAND1 Enhancer Variation Impacts Heart Conduction
     
    Zhuang, et al. EC-Klf2-Foxp1-Nlrp3 Regulates Atherogenesis
     
    Quintanilla, et al. Robust Targets for Persistent AF Ablation
     
    Lambert et al. Characterization of Kcnk3-Mutated Rats
     
    Myagmar et al. Gq Mediates Cardioprotection
    Transcript
    Cindy St. H:       Hi, welcome to Discover CircRes, the monthly podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you highlights from recent articles published in the August 30th and September 13th issues of Circulation Research. We'll also have an in-depth conversation with Drs. Matthew Stratton, Rushita Bagchi, and Tim McKinsey, who are the lead authors of one of the exciting discoveries presented in the September 13th issue.
    Cindy St. H:         The first article I want to share with you is titled, "Variation in a Left Ventricle–Specific Hand1 Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function." The first author is Joshua Vincentz and the corresponding author is Anthony Firulli, and this work was conducted in the Departments of Pediatrics, Anatomy, and Medical and Molecular Genetics at Indiana Medical School in Indianapolis, Indiana.
    Cindy St. H:         The heart's ventricular conduction system, or VCS, is composed of specialized muscle cells that propagate electrical signals through the working myocardium of the ventricles to coordinate the rhythmic contractions of the heart chambers. Disorders of the VCS can lead to certain types of arrhythmia. Genome-wide association studies have identified a number of single nucleotide polymorphisms, or SNPs, that appear to increase the risk of VCS-mediated arrhythmias. Two such SNPs are located in the upstream region of a gene encoding for Hand1. And Hand1 is a transcription factor that is involved in left ventricle development. Conditional cardiac Hand1 ablation during embryogenesis leads to ventricular septal defects and hyperplastic arterial ventricular valves, and a reduction in Hand1 expression could lead to morphological, and therefore functional defects.

    Vincentz and colleagues hypothesized that these SNPs might reside in an enhancer element, and that's a region of DNA and a promoter that allows for the increased expression of a gene. The region containing the SNPs is highly conserved from mammals to reptiles and includes two sequences that allow for the binding of GATA transcription factors. And GATA transcription factors are well known to drive cardiac development. So this team used CRISPR-Cas9 technology to show that the deletion of the enhancer impaired normal VCS morphology and therefore function. And they did this in a mouse model and in the in vitro electromobility shift assay (which frankly was one of my favorite love-to-hate experiments of my PhD). So this group did their own electromobility shift essay and showed that GATA-4 binds to these enhancer sites. And together, these results support a role for Hand1 in the formation and function of the VCS and offer insights to possible arrhythmia etiologies.

    And what I really love about this paper is that they could actually go from a SNP in a GWAS to a functional role of a protein, which is great. A lot of times with GWAS studies, you have no clue what the heck is going on. So this was a beautiful study where they actually coul

    • 36 min
    August 2019 Issue

    August 2019 Issue

     
    This month on the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from recent issues of Circulation Research and talks with Denisa Wagner and Nicoletta Sorvillo about their article on how PAD4 in blood promotes VWF strings and thrombosis.
    Article highlights:
    Goodyer et al: ScRNA-seq of the Cardiac Conduction System
     
    Xiong et al: Chemotaxis Mediated Second Heart Field Deployment
     
    Ranchoux et al: Pulmonary Hypertension and Metabolic Syndrome
     
    Rühl et al. Thrombin/APC Response in FVL and FII 20210G>A
     
    Mahmoud et al. LncRNA SMILR’s Mechanism and Therapeutic Potential
     
    Transcript
     
    Cindy St. H:                         Hi, welcome to Discover CircRes, the monthly podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Cindy St. Hilaire, and I'm an assistant professor at the University of Pittsburgh. My goal as host of this podcast is to share with you some highlights from the recent articles published in the August 2nd and August 16th issues of Circulation Research.
    Cindy St. H:                         After I discuss some highlights, we'll also have an in-depth conversation with Drs. Denisa Wagner and Nicoletta Sorvillo, from Boston Children's Hospital and Harvard Medical School, who are the lead authors of one of the exciting discoveries from the August 16th issue.
    Cindy St. H:                         The first article I want to share with you today is titled Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution. The first author is William R. Goodyer, and the corresponding author is Sean Wu. They are both located at the Cardiovascular Institute and the Department of Pediatrics at Stanford University.
    Cindy St. H:                         Have you ever wondered how your heart beats, and why there's always this glub-glub pattern, and where did it come from? How is the heart able to initiate that pattern, from cells that don't contract to cells that contract? Well, the beating of the heart is regulated by what's called the cardiac conduction system, and this is an area in the heart of specialized cells, and these cells establish the rhythmic beating by coordinating the contraction of the chambers of the heart.
    Cindy St. H:                         There's several components to the CSS. The sinoatrial node acts as the pacemaker in the right atrium. The arterial ventricle node is the electrical relay that slows down the pulse from the SA node. A His bundle helps to transmit those impulses, and the Purkinjie fibers are the terminus of the electrical signal. Between all of these different components are a heterogeneous population of what are called transitional cells. There are several studies that have linked these somewhat amorphous or heterogeneous transitional cells to different arrhythmic disorders.
    Cindy St. H:                         For the normal function of the heart, all of these parts must come together, and when they don't, there's severe clinical manifestations such as arrhythmias, like I said, but also you can get decreased cardiac output and even sudden cardiac death. While important, the cells of the CSS are rather elusive, and that's because they're in a relatively small number compared to the rest of the cells in the heart, and there also aren't very clear markers to identify the cells in the CSS.
    Cindy St. H:                         To address this, Goodyer and colleagues harvested cells from embryonic mouse hearts and performed single-cell RNA sequencing on 22,000 individually barcoded cells. What they were looking for is learning what type of cells they are, but more importantly, they had the goal of ide

    • 31 min

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