Circulatory and Respiratory Physiology Commons^™

Vascular Medicine: A ‘Primary’ Specialty, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

N/A

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations & Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Telemetric Blood Pressure Assessment In Angiotensin Ii-Infused Apoe-/- Mice: 28 Day Natural History And Comparison To Tail-Cuff Measurements, Christopher M. Haggerty, Andrea C. Mattingly, Ming C. Gong, Wen Su, Alan Daugherty, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of …

Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn

Electronic Thesis and Dissertation Repository

The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD⁺, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD⁺ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD⁺ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD⁺ levels, establishing PARP in NAD⁺ consumption in this …

Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction, Laura L. Daniel

Electronic Theses and Dissertations

Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects …

Novel Techniques For Investigating The Regulation Of Skeletal Muscle Hemodynamics, Baraa K. Al-Khazraji

Electronic Thesis and Dissertation Repository

The effect of the sympathetic nervous system (SNS) on blood flow distribution within skeletal muscle microvasculature is conditional upon regional activation of SNS receptors. Due to a lack of appropriate experimental models and techniques, no study has systematically evaluated the effect of SNS receptor activation in continuously branching skeletal muscle arteriolar trees. In line with previous work, we hypothesize that there will be a spatially-dependent distribution of sympathetic receptor activation along the arteriolar tree. Specifically, we anticipate a progressive decrease of adrenergic activation and a progressive increase of peptidergic and purinergic activation with increasing arteriolar order. We developed a novel …

Timp3 Regulation Of Macrophage Activation And Apoptosis, Michael S. Brock

Electronic Thesis and Dissertation Repository

Acute respiratory distress syndrome (ARDS) is a lung disease involving profound inflammation. Origins of persistent inflammation in select cases of ARDS are poorly understood, and we propose persistent inflammatory macrophages may be one of its mechanisms. Macrophages polarize to either promote inflammation, or suppress inflammation. Tissue inhibitor of metalloproteinases 3 (TIMP3) reduces the pro-inflammatory polarization in macrophages. Additionally, studies have shown TIMP3 promotes apoptosis, and its absence delays recovery from bleomycin-induced lung injury.

We hypothesize that TIMP3 promotes apoptosis of murine macrophages through inhibition of metalloproteinase activity and stabilization of FAS on the cell surface. Pro-inflammatory Timp3^-/- bone marrow-derived …

Is Early Broncoscopy Helpful In Diagnosing Inhalation Injury?, Sigrid Blome-Eberwein

Sigrid A Blome-Eberwein MD

No abstract provided.

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Daniels

Dr. Christopher C Daniels

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …

Validation Of In Vivo 2d Displacements From Spiral Cine Dense At 3t, Gregory J. Wehner, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David K. Powell, Sean M. Hamlet, Jonathan D. Grabau, Walter Dimitri Mojsejenko, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. Due to the stimulated echo, the signal is inherently low and fades through the cardiac cycle. To compensate, a spiral acquisition has been used at 1.5T. This spiral sequence has not been validated at 3T, where the increased signal would be valuable, but field inhomogeneities may result in measurement errors. We hypothesized that spiral cine DENSE is valid at 3T and tested this hypothesis by measuring displacement errors at both 1.5T and 3T in vivo.

METHODS: Two-dimensional spiral cine DENSE and tagged …

The Tmao-Generating Enzyme Flavin Monooxygenase 3 Is A Central Regulator Of Cholesterol Balance, Manya Warrier, Diana M. Shih, Amy C. Burrows, Daniel Ferguson, Anthony D. Gromovsky, Amanda L. Brown, Stephanie Marshall, Allison Mcdaniel, Rebecca C. Schugar, Zeneng Wang, Jessica Sacks, Xin Rong, Thomas De Aguiar Vallim, Jeff Chou, Pavlina T. Ivanova, David S. Myers, H. Alex Brown, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Xiuli Liu, Paolo Parini, Peter Tontonoz, Aldon J. Lusis, Stanley L. Hazen, Ryan E. Temel, J. Mark Brown

Saha Cardiovascular Research Center Faculty Publications

Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress …

Reactive Hyperemia Occurs Via Activation Of Inwardly-Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno

Anne R. Crecelius

Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear. Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na+/K+-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans. Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 …

Surfactant And Matrix Metalloproteinase 3 In The Pathogenesis Of Acute Lung Injury, Valeria Puntorieri

Electronic Thesis and Dissertation Repository

Acute lung injury (ALI) is a pulmonary inflammatory disorder resulting in respiratory failure that is initiated by a number of different insults to the lung. Despite very high mortality, there are still no effective treatments for this disease, and the main supportive therapy, mechanical ventilation, can further lung injury and contribute to ALI progression. The overall objective of this work was therefore to evaluate the role of two key players in the disease process, such as: i) lung surfactant, a material essential for minimizing the work of breathing and for pulmonary immunomodulation, and ii) matrix metalloproteinase 3 (MMP-3), protease involved …

Inverse Relationship Between Physical Activity, Adiposity And Arterial Stiffness In Healthy Middle-Aged Subjects, Oscar Mac Ananey, B Mc Loughlin, A Leonard, L Maher, P Gaffney, G Boran, V Maher

Articles

BACKGROUND:

Several obesity related factors are reported to exacerbate premature arterial stiffening, including inactivity and metabolic disarray. The aim of the present study was to investigate the relationship between physical activity, arterial stiffness and adiposity using objective methods. To further explore the role of adiposity in this complex process, obesity associated anthropometric and humoral biomarkers were measured.

METHODS:

Seventy-nine healthy, lifelong non-smoking, subjects were recruited. Habitual physical activity was measured using accelerometry. Arterial stiffness (augmentation index; AIx & pulse wave velocity; PWV), was measured using tonometry. Body composition was estimated using bioimpedence. Adipose associated biomarkers, leptin and adiponectin, were also …

Inhibition Of Mtor Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction, Scott M. Filippone

Theses and Dissertations

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of …

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …

One Year Review Of High Flow Oxygen Delivery System Outcomes, Susan Carvin Rrt-Accs, Kenneth Miller Med, Rrt-Nps, Diane Horoski, Robert Leshko Bs,Rrt, Rita Pechulis Md, Fccp

Patient Care Services / Nursing

No abstract provided.

Analysis Of Drug Interactions With Lipoproteins By High Performance Affinity Chromatography, Matthew R. Sobansky

Department of Chemistry: Dissertations, Theses, and Student Research

High density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) are lipoproteins previously shown to bind many basic and neutral hydrophobic drugs in serum. These interactions impact the distribution, delivery, metabolism, and excretion of drugs and are important in determining drug activity, pharmacokinetics, and toxicity in the human body. Information about drug-lipoprotein interactions and the strength of these interactions can be useful in determining the distribution of drugs following administration.

The research presented in this dissertation uses high performance affinity chromatography (HPAC) and packed columns to study binding of the drug propranolol to immobilized lipoproteins such …

Simplified Post Processing Of Cine Dense Cardiovascular Magnetic Resonance For Quantification Of Cardiac Mechanics, Jonathan D. Suever, Gregory J. Wehner, Christopher M. Haggerty, Linyuan Jing, Sean M. Hamlet, Cassi M. Binkley, Sage P. Kramer, Andrea C. Mattingly, David K. Powell, Kenneth C. Bilchick, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Cardiovascular magnetic resonance using displacement encoding with stimulated echoes (DENSE) is capable of assessing advanced measures of cardiac mechanics such as strain and torsion. A potential hurdle to widespread clinical adoption of DENSE is the time required to manually segment the myocardium during post-processing of the images. To overcome this hurdle, we proposed a radical approach in which only three contours per image slice are required for post-processing (instead of the typical 30-40 contours per image slice). We hypothesized that peak left ventricular circumferential, longitudinal and radial strains and torsion could be accurately quantified using this simplified analysis.

METHODS …