Cardiology Commons^™

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Polygenic Risk, Midlife Life's Simple 7, And Lifetime Risk Of Stroke, Emy A Thomas, Nitesh Enduru, Adrienne Tin, Eric Boerwinkle, Michael E Griswold, Thomas H Mosley, Rebecca F Gottesman, Myriam Fornage

Faculty, Staff and Student Publications

Background

Recent genetic discoveries in stroke have unleashed the potential of using genetic information for risk prediction and health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels of genetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime risk of stroke.

Methods and Results

Study participants were 11 568 middle‐aged adults (56% women, 23% Black adults), who were free of stroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels …

Rationale And Design Of Savi-Aos: A Physiologic Study Of Patients With Symptomatic Moderate Aortic Valve Stenosis And Preserved Left Ventricular Ejection Fraction, Rob Eerdekens, Pim Tonino, Jo Zelis, Rik Adrichem, Jung-Min Ahn, Jesse Demandt, Ashkan Eftekhari, Mohamed El Farissi, Phillip Freeman, Abdul Rahman Ihdayhid, Nikolaos Kakouros, Dae-Hee Kim, Seung-Ah Lee, Nicolas M Van Mieghem, Waqas Qureshi, Nils P Johnson

Faculty, Staff and Student Publications

Background: Moderate aortic valve stenosis occurs twice as often as severe aortic stenosis (AS) and carries a similarly poor prognosis. Current European and American guidelines offer limited insight into moderate AS (MAS) patients with unexplained symptoms. Measuring valve physiology at rest while most patients experience symptoms during exertion might represent a conceptual limitation in the current grading of AS severity. The stress aortic valve index (SAVI) may delineate hemodynamically significant AS among patients with MAS.

Objectives: To investigate the diagnostic value of SAVI in symptomatic MAS patients with normal left ventricular ejection fraction (LVEF ≥ 50%): aortic valve area (AVA) …

Association Of Cardiovascular Health Through Young Adulthood With Genome-Wide Dna Methylation Patterns In Midlife: The Cardia Study, Yinan Zheng, Brian T Joyce, Shih-Jen Hwang, Jiantao Ma, Lei Liu, Norrina B Allen, Amy E Krefman, Jun Wang, Tao Gao, Drew R Nannini, Haixiang Zhang, David R Jacobs, Myron D Gross, Myriam Fornage, Cora E Lewis, Pamela J Schreiner, Stephen Sidney, Dongquan Chen, Philip Greenland, Daniel Levy, Lifang Hou, Donald M Lloyd-Jones

Faculty, Staff and Student Publications

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD.

Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was …

Prolonged Cardiac Nr4a2 Activation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Comparison Of Different Metrics Of Cerebral Autoregulation In Association With Major Morbidity And Mortality After Cardiac Surgery, Xiuyun Liu, Joseph Donnelly, Ken M Brady, Kei Akiyoshi, Brian Bush, Raymond C Koehler, Jennifer K Lee, Charles W Hogue, Marek Czosnyka, Peter Smielewski, Charles H Brown

Faculty, Staff and Student Publications

BACKGROUND: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery.

METHODS: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. …

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Jesse Chait, Emanuel R Tenorio, Bernardo C Mendes, Guilherme B Barbosa Lima, Giulianna B Marcondes, Joshua Wong, Thanila A Macedo, Randall R De Martino, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …

Cardiovascular Disease Awareness Program On Risk Factors For Cardiovascular Disease Among Adolescents In Selected Schools, In New Delhi, Komal Kumari

Manipal Journal of Nursing and Health Sciences

Introduction: Cardiovascular disease (CVD) is the main cause of mortality worldwide. The main risk factors include tobacco chewing/smoking, higher blood cholesterol, high blood pressure, physical inactivity, obesity, excessive alcohol use, age, sex, and heredity. Although CVDs commonly develop in middle age or later, risk factors are highly impacted by childhood practices that are continued into maturity. Knowledge gaps on CVD and its risk factors are major obstacles to effective prevention and treatment. Hence, a CVD awareness program was organized in order to educate adolescents about CVD and its risk factors. Objective: The objectives of the study were to identify students’ …

Sinus Pauses And Asystole As A Rare Presentation Of Thyrotoxic Crisis: A Case Report, Christian Akem Dimala, Charnjeet Sandhu, Oreoluwa Oladiran, Agnieszka Mochon, William Finneran Iii

Transformative Medicine

Introduction

Thyroid crisis is a rare and life-threatening endocrine emergency characterized by exaggerated clinical manifestations of hyperthyroidism with cardiovascular manifestations being the most severe. Rhythm disturbances, sinus tachycardia and atrial fibrillation, are the commonest cardiac manifestations of severe thyrotoxicosis; however, asystole remains a very atypical and uncommon presentation. We present a case of thyrotoxicosis due to Grave’s disease complicated by multiple episodes of asystole.

Case Presentation

A 65-year-old female recently diagnosed with Grave’s disease presented to the hospital with recurrent episodes of syncope. Her hospital course was significant for atrial fibrillation with subsequent progression to sinus pauses and asystole spontaneously …

Associations Between Adherence To The Dietary Approaches To Stop Hypertension (Dash) Diet And Six Glucose Homeostasis Traits In The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Gautam Ramesh, Alexis C Wood, Matthew A Allison, Stephen S Rich, Elizabeth T Jensen, Yii-Der I Chen, Jerome I Rotter, Alain G Bertoni, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Background and aims: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components.

Methods and results: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) …

1485-Pub: Assessing Correlates Of Microvascular Complications Among Patients With Diabetes Mellitus, Kenneth Izuora, Amalie Alver, Arpita Basu, Kavita Batra, Shelley J. Williams, Jeffrey L. Ebersole

Department of Internal Medicine Faculty Research

Background: Microvascular complications associated with diabetes (DM) are important predictors of morbidity and mortality. Understanding the factors associated with these complications is important in reducing their burden. Method: Using a cross-sectional study design, seventy-one ambulatory patients with Type 2 DM (female 60.6%, white 36.6%, mean age 64.1± 10.3 years, and mean duration of DM 15.8±9.1 years) were recruited using an investigator-administered questionnaire and chart review. Variables of demographics, smoking, HbA1c, DM duration, and complications were collected. CRP was measured and oral health status was assessed by a clinical exam. Data were analyzed using Chi-square/Fisher exact tests and binomial logistic regression …

Multi-Phenotype Analyses Of Hemostatic Traits With Cardiovascular Events Reveal Novel Genetic Associations, Gerard Temprano-Sagrera, Colleen M Sitlani, William P Bone, Miguel Martin-Bornez, Benjamin F Voight, Alanna C Morrison, Scott M Damrauer, Paul S De Vries, Nicholas L Smith, Maria Sabater-Lleal

Faculty, Staff and Student Publications

BACKGROUND: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.

OBJECTIVES: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events.

METHODS: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen …

Effect Of Calcium Chloride And Isoflurane On Force Frequency Relationship In Canines, Harrison Patrizio, Lawrence Mulligan

Rowan-Virtua Research Day

Proper calcium cycling is critical for a optimally functioning heart.

Improper calcium cycling in humans can contribute to heart failure.

Human calcium cycling is difficult to study due to the risks of damaging the patient’s cardiac tissue.

Risk of further damaging cardiac tissue is substantially increased in a heart failure patient.

Past studies focus on studying the effects of changing calcium cycling in lab rats.

Current research shows limited alternative methods in studying relationships between calcium cycling and FFR in larger mammals.

This project analyzes data to determine the response of the canine force frequency relationship to calcium chloride and …

An Evaluation Of Oral Anticoagulation Initiation After Ischemic Stroke In Patients With Atrial Fibrillation/Atrial Flutter At Hospital Discharge, Jessica Zhao, Meri Slavica, Vanessa Jenkins, Natalie Swearingen

Providence Pharmacy PGY1 Program at Providence Portland and Providence St. Vincent Medical Centers 2022

No abstract provided.

Mechanism Of Rare Variant In Acta2, P.Arg149cys, Driving Diverse Vascular Disease, Kaveeta Kaw

Dissertations and Theses (Open Access)

Heterozygous variants in ACTA2 (smooth muscle (SM) α-actin) predispose to thoracic aortic aneurysms and dissections (TAAD) and early-onset coronary artery disease (CAD). The most common ACTA2 mutation is a genetic alteration of arginine 149 to a cysteine, ACTA2 p.Arg149Cys, which accounts for disease in 24% of all ACTA2 mutation carriers.(1) ACTA2 p.Arg149Cys mutation carriers present with either TAAD or CAD but rarely have both diseases. To identify the molecular mechanisms dictating whether an individual with ACTA2 p.Arg149Cys develops TAAD or CAD, CRISPR/Cas9 technology was used to generate the mutant mouse, Acta2^R149C/+, in a C57BL6 background. Acta2^R149C/+ mice …

Free Cholesterol Bioavailability And Atherosclerosis, Rei J Abe, Jun-Ichi Abe, Minh T H Nguyen, Elizabeth A Olmsted-Davis, Abrar Mamun, Priyanka Banerjee, John P Cooke, Longhou Fang, Henry Pownall, Nhat-Tu Le

Faculty, Staff and Student Publications

Purpose of review: As both a cholesterol acceptor and carrier in the reverse cholesterol transport (RCT) pathway, high-density lipoprotein (HDL) is putatively atheroprotective. However, current pharmacological therapies to increase plasma HDL cholesterol (HDL-c) concentration have paradoxically failed to prevent or reduce atherosclerosis and cardiovascular disease (CVD). Given that free cholesterol (FC) transfer between surfaces of lipoproteins and cells is reversible, excess plasma FC can be transferred to the cells of peripheral tissue sites resulting in atherosclerosis. Here, we summarize potential mechanisms contributing to this paradox and highlight the role of excess free cholesterol (FC) bioavailability in atherosclerosis vs. atheroprotection.

Recent …

Identification Of Genetic Loci Simultaneously Associated With Multiple Cardiometabolic Traits, Alexis C Wood, Amit Arora, Michelle Newell, Victoria L Bland, Jin Zhou, Nicola Pirastu, Jose M Ordovas, Yann C Klimentidis

Children’s Nutrition Research Center Staff Publications

Background and aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.

Methods and results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple …

Breaks In Longitudinal Elastic Fibers Of Human Femoropopliteal Arteries, Elham Zamani

UNO Student Research and Creative Activity Fair

Breaks in Longitudinal Elastic Fibers of Human Femoropopliteal Arteries

Elham Zamani1, Majid Jadidi1

1 Department of Biomechanics, University of Nebraska Omaha, Omaha, NE

Introduction: Elastin is a major protein in the body with half-life >50 years. It is thought that elastic fibers are formed before the postnatal period. In the femoropopliteal artery (FPA), the main artery in the leg, longitudinal elastic fibers are present in External Elastic Lamina (EEL). Our team has studied more than 1000 cadaveric human FPA and has noticed that there are big breaks in their longitudinal elastic fibers in some subjects. Our goal in this work …

Imaging Techniques For Aortic Aneurysms And Dissections In Mice: Comparisons Of Ex Vivo, In Situ, And Ultrasound Approaches, Sohei Ito, Hong S. Lu, Alan Daugherty, Hisashi Sawada

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysms and dissections are life-threatening conditions that have a high risk for lethal bleeding and organ malperfusion. Many studies have investigated the molecular basis of these diseases using mouse models. In mice, ex vivo, in situ, and ultrasound imaging are major approaches to evaluate aortic diameters, a common parameter to determine the severity of aortic aneurysms. However, accurate evaluations of aortic dimensions by these imaging approaches could be challenging due to pathological features of aortic aneurysms. Currently, there is no standardized mode to assess aortic dissections in mice. It is important to understand the characteristics of each approach for …

Obstructive Sleep Apnea And Cardiovascular Disease, Evan Gagnon

Graduate Research Projects

No abstract provided.

Effects Of Tamoxifen Inducible Mercremer On Gene Expression In Cardiac Myocytes In Mice, Leila Rouhi, Siyang Fan, Sirisha M Cheedipudi, Melis Olcum, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM (Myh6-Mcm) mice for 5 consecutive days. Cardiac function, myocardial histology, and gene expression (RNA-sequencing) were analyzed 2 weeks after TAM injection. A total of 346 protein coding genes (168 up- and 178 down-regulated) were differentially expressed. Transcript levels of 85 genes, analyzed …

Kidney Disease After Heart And Lung Transplantation, Carlos M Zapata, Hassan N Ibrahim

Faculty, Staff and Student Publications

Chronic kidney disease (CKD) is not only common after lung and heart transplantation but also is associated with increased morbidity and mortality due to multiple pre-, peri- and post-transplant factors. While the exact incidence of CKD in this population is not well-defined, it seems to have gradually increased over the years as older recipients are more frequently considered. The increasing success of the procedure and expanding transplant candidate pool has allowed many with comorbid conditions to receive a transplant, which was considered prohibitive in the past. This review presents risk factors that have been linked to CKD as well as …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Cancer Treatment-Induced Nad+ Depletion In Premature Senescence And Late Cardiovascular Complications, Priyanka Banerjee, Elizabeth A Olmsted-Davis, Anita Deswal, Minh Th Nguyen, Efstratios Koutroumpakis, Nicholas L Palaskas, Steven H Lin, Sivareddy Kotla, Cielito Reyes-Gibby, Sai-Ching J Yeung, Syed Wamique Yusuf, Momoko Yoshimoto, Michihiro Kobayashi, Bing Yu, Keri Schadler, Joerg Herrmann, John P Cooke, Abhishek Jain, Eduardo Chini, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family …

Serum Gamma Glutamyltransferase (Ggt) In Coronary Artery Disease: Exploring The Asian Indian Connection, Kunal K Singh, Aditya Kapoor, Roopali Khanna, Ankit Sahu, Vishwas Kapoor, Sudeep Kumar, Naveen Garg, Satyendra Tewari, Pravin Goel

Faculty, Staff and Student Publications

BACKGROUND: There is a need to identify novel markers for CAD, independent of traditional CV risk factors. One of these is gamma-glutamyl transferase (GGT), a marker of increased oxidative stress. Given the high prevalence of CAD in Asian Indians, the link of GGT and CAD in them needs to be studied.

AIM: To assess GGT in patients with angiographically documented CAD.

METHODS AND RESULTS: Two hundred patients aged 58.1 ± 9.95 years, 73% males, hypertension 56%, diabetes 40% were included. Mean GGT was 63.6 ± 44.33 (10–269 U/L). The levels of GGT progressively increased in those with single/double or triple-vessel …

Clinicopathological Correlations In Heart Transplantation Recipients Complicated By Death Or Re-Transplantation, Michelle M Mcdonald, Maks Mihalj, Bihong Zhao, Sriram Nathan, Stanislava Matejin, Giulia Ottaviani, Mateja K Jezovnik, Rajko Radovancevic, Biswajit Kar, Igor D Gregoric, L Maximilian Buja

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation.

METHODOLOGY AND STUDY DESIGN: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were …

Evaluation Of Contemporary Echocardiographic And Histomorphology Parameters In Predicting Mortality In Patients With Endomyocardial Biopsy-Proven Cardiac Al Amyloidosis, Efstratios Koutroumpakis, Adam Niku, Christopher K Black, Abdelrahman Ali, Humaira Sadaf, Juhee Song, Nicolas Palaskas, Cezar Iliescu, Jean-Bernard Durand, Syed Wamique Yusuf, Hans C Lee, L Maximilian Buja, Anita Deswal, Jose Banchs

Faculty, Staff and Student Publications

INTRODUCTION: This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis.

METHODS: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization.

RESULTS: Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (

CONCLUSION: Lower LA strain …

Myeloid Hypoxia-Inducible Factor Hif1a Provides Cardio-Protection During Ischemia And Reperfusion, Ka Lin Heck-Swain, Jiwen Li, Wei Ruan, Xiaoyi Yuan, Yanyu Wang, Michael Koeppen, Holger K Eltzschig

Faculty, Staff and Student Publications

The transcription factor hypoxia-inducible factor HIF1A induces cardioprotection from ischemia and reperfusion injury. Here, we investigate tissue-specific pathways that are critical for HIF1A-elicited tissue protection. Initial studies showed that mice with induced global Hif1a deletion (Hif1aloxP/loxP UbiquitinCre+) have exaggerated myocardial injury during in situ ischemia and reperfusion. Surprisingly, this phenotype was mirrored only in mice with myeloid-specific Hif1a deletion (Hif1aloxP/loxP LysM Cre+). In contrast, mice with myocardial specific (Hif1aloxP/loxP Myosin Cre+), or vascular Hif1a deletion (Hif1aloxP/loxP VEcadherin Cre+) experienced similar levels of injury as controls. Subsequent studies using adoptive transfer of Hif1a-deficient polymorphonuclear neutrophils (PMNs) …

The Wnt/Β-Catenin Pathway Regulates Expression Of The Genes Involved In Cell Cycle Progression And Mitochondrial Oxidative Phosphorylation In The Postmitotic Cardiac Myocytes, Melis Olcum, Sirisha M Cheedipudi, Leila Rouhi, Siyang Fan, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types. The effects of the cWNT pathway on the expression of genes involved in cell cycle reentry in the postmitotic cardiac myocytes are unknown.

AIM: The aim of the study was to identify genes whose expression is regulated by the β-catenin, the indispensable component to the cWNT signaling, in the postmitotic myocytes.

METHODS AND RESULTS: …

Magi1 Inhibits Interferon Signaling To Promote Influenza A Infection, Yin Wang, Jun-Ichi Abe, Khanh M Chau, Yongxing Wang, Hang Thi Vu, Loka Reddy Velatooru, Fahad Gulraiz, Masaki Imanishi, Venkata S K Samanthapudi, Minh T H Nguyen, Kyung Ae Ko, Ling-Ling Lee, Tamlyn N Thomas, Elizabeth A Olmsted-Davis, Sivareddy Kotla, Keigi Fujiwara, John P Cooke, Di Zhao, Scott E Evans, Nhat-Tu Le

Faculty, Staff and Student Publications

We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may …