Cardiology Commons^™

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

The Role Of The Erbb Signaling Pathway In Cardiovascular Progenitor Cell-Based Repair, Christopher Ramos

Electronic Theses, Projects, and Dissertations

Adult mammalian hearts lack self-renewal and proliferative capabilities necessary for cardiovascular regeneration. Current treatments using cardiac progenitor cells (CPCs) for cell-based repair do not restore cardiac function in patients who experience a myocardial infarction (MI). Our laboratory has been studying Islet-1+ neonatal CPCs as a promising candidate for cell-based repair due to their ability to significantly improve cardiac function after MI in sheep. The current study addresses the hypothesis that the ERBB pathway is linked to the Hippo-pathway to activate YAP1 by the involvement of an autocrine loop that upregulates neuregulin (NRG). In our sheep model of MI and cardiovascular …

One Amino Acid Change Of Angiotensin Ii Diminishes Its Effects On Abdominal Aortic Aneurysm, Ya Wang, Yinchuan Xu, Congqing Wu, Hongguang Xia, Yingchao Wang, Jinliang Nan, Jinghai Chen, Hong Yu, Wei Zhu, Peng Shi, Alan Daugherty, Hong S. Lu, Jian'an Wang

Saha Cardiovascular Research Center Faculty Publications

Angiotensin (Ang) A is formed by the decarboxylation of the N terminal residue of AngII. The present study determined whether this one amino acid change impacted effects of AngII on abdominal aortic aneurysm (AAA) formation in mice. Computational analyses implicated that AngA had comparable binding affinity to both AngII type 1 and 2 receptors as AngII. To compare effects of these two octapeptides in vivo, male low-density lipoprotein receptor (Ldlr) or apolipoprotein E (Apoe) deficient mice were infused with either AngII or AngA (1 μg/kg/min) for 4 weeks. While AngII infusion induced AAA consistently in …

Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Quantum Confined Peptide Assemblies With Tunable Visible To Near-Infrared Spectral Range, Kai Tao, Zhen Fan, Leming Sun, Pandeeswar Makam, Zhen Tian, Mark Ruegsegger, Shira Shaham-Niv, Derek Hansford, Ruth Aizen, Zui Pan, Scott Galster, Jianjie Ma, Fan Yuan, Mingsu Si, Songnan Qu, Mingjun Zhang, Ehud Gazit, Junbai Li

Faculty & Staff Scholarship

Quantum confined materials have been extensively studied for photoluminescent applica- tions. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio- imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for …

Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast

Gill Heart & Vascular Institute Faculty Publications

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, …

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Department of Biochemistry: Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation …

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Nader G. Abraham, Joseph I Shapiro

Nader G. Abraham

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Nader G. Abraham, Joseph I Shapiro

Jiang Liu

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

Omecamtiv Mecarbil Enhances The Duty Ratio Of Human Β-Cardiac Myosin Resulting In Increased Calcium Sensitivity And Slowed Force Development In Cardiac Muscle, Anja M. Swenson, Wanjian Tang, Cheavar A. Blair, Christopher M. Fetrow, William C. Unrath, Michael J. Previs, Kenneth S. Campbell, Christopher M. Yengo

Physiology Faculty Publications

The small molecule drug omecamtiv mecarbil (OM) specifically targets cardiac muscle myosin and is known to enhance cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear. We expressed and purified human β-cardiac myosin subfragment 1 (M2β-S1) containing a C-terminal Avi tag. We demonstrate that the maximum actin-activated ATPase activity of M2β-S1 is slowed more than 4-fold in the presence of OM, whereas the actin concentration required for half-maximal ATPase was reduced dramatically (30-fold). We find OM does not change the overall actin affinity. Transient kinetic experiments suggest that there are …

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Nader G. Abraham, Joseph Shapiro

NYMC Faculty Publications

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

Steroid Binding To Autotaxin Links Bile Salts And Lysophosphatidic Acid Signalling, Willem-Jan Keune, Jens Hausmann, Ruth Bolier, Dagmar Tolenaars, Andreas Kremer, Tatjana Heidebrecht, Robbie P. Joosten, Manjula Sunkara, Andrew J. Morris, Elisa Matas-Rico, Wouter H. Moolenaar, Ronald P. Oude Elferink, Anastassis Perrakis

Gill Heart & Vascular Institute Faculty Publications

Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7α-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors …

Background Differences In Baseline And Stimulated Mmp Levels Influence Abdominal Aortic Aneurysm Susceptibility, Matthew A. Dale, Melissa K. Suh, Shijia Zhao, Trevor Meisinger, Linxia Gu, Vicki J. Swier, Devendra K. Agrawal, Timothy Greiner, Jeffrey S. Carson, B. Timothy Baxter, Wanfen Xiong

Department of Mechanical and Materials Engineering: Faculty Publications

Objective: Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression.

Methods: Mice of C57Bl/6 or 129/SvEv background underwent AAA induction …

Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus

Victor R. Ambros

BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia. METHODS: Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin

Dissertations & Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …