Cardiovascular Diseases Commons^™

Mechanical Characterization And Modeling Of Rat Myocardia Under The Influence Of Epirubicin, Abdallah Mahmoud Alkhaiyat

Theses and Dissertations

Cancer remains a predominant health challenge that is responsible for a significant portion of global morbidity and mortality. Epirubicin (EPI), a chemotherapeutic anti-cancer drug, has shown remarkable efficacy in combating various malignancies. However, it is known to have undesirable side effects on the heart, collectively referred to as cardiotoxicity. This research investigates the adverse effects of chemotherapy on cardiac contractility through an in vitro examination of the mechanics of healthy and infarcted animal heart tissues. Electrically stimulated slices of rat ventricular tissue were tested using an isometric force measurement tissue bath. The tissue slices were subjected to uniaxial stretching, allowing …

Metabolic Syndrome Beyond Diagnostic Criteria: Population-Scale Integrative Metabolomics Characterization, Marwa Talal

Theses and Dissertations

Background: Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic abnormalities associated with elevated cardiometabolic risk. While diagnosis is based on well-established five clinical criteria, these may overlook early or atypical metabolic alterations. Large-scale metabolomic profiling offers an opportunity to identify biochemical signatures of MetS beyond diagnostic bias and to evaluate their relative importance across different presentations of the syndrome.

Methods: Data from 117,147 UK Biobank participants were analyzed in a cross-sectional design. High-throughput NMR quantified 75 circulating metabolites, for. Univariate analyses, MetS subtype stratification, and elastic net models with SHAP interpretation were applied to assess feature …

Pricks And Pills, Anna A. Charles

Theses and Dissertations

"Pricks and Pills" is a collection of audio pieces designed for an online platform where individuals with diabetes can listen to and find emotional support from others who share their experiences. This audio project provides an intimate look into the lives of people navigating the challenges of diabetes. Through heartfelt interviews with individuals and their families, the podcast highlights their journeys, showcasing both their struggles and triumphs.

Chronobiology Of Meal Timing In Early-Stage Hypertension: Effects On Renal And Vascular Function, Natalie J. Bohmke

Theses and Dissertations

Introduction: Previous research determined that a Western-style meal acts as a stressor to the kidney and contributed to impaired blood pressure and vascular function. Despite an understanding of acute postprandial physiology in humans, studies have not investigated the impact of the time of day of meal consumption on physiology. Methods: Ten participants with elevated or stage-one hypertension underwent a randomized crossover trial with a controlled feeding intervention of a Western-style meal in the morning or the evening. Participants completed a run-in day to standardize diet followed by the experimental day. On day 2, participants completed ambulatory blood pressure, core temperature, …

Cardiometabolic Genomics And Pharmacogenomics In Filipino Americans: A Cross-Sectional Study, Khalifa Y. Alrajeh

Theses and Dissertations

Background: Heart disease remains a leading cause of death in the country, with significant ethnic disparities. Filipino Americans (FAs), the third-largest Asian subgroup in U.S., face an elevated burden of dyslipidemia, a primary modifiable risk factor for heart disease. Objectives: This community-based study addresses critical knowledge gaps by characterizing the cardiometabolic and genetic factors contributing to dyslipidemia among FAs and implications for personalized cardiovascular drug therapies, particularly statin pharmacogenomics (PGx). Methods: We characterized dyslipidemia prevalence in FAs and major ethnic subgroups using nationally representative NHANES data. We examined associations between uric acid (UA) levels and lipid profiles, …

Effectiveness Of Intervention Studies Based On Diet And/Or Physical Activity In Treatment, Prevention, And Management Of Diabetes Among South Asians: A Systematic Review, Ishaan Arora

Theses and Dissertations

The purpose of this study was to describe diet and/or physical activity-based interventions and their control in cardiometabolic risk factors of diabetes for the South Asian (SA) population. A systematic review was conducted in accordance with the PRISMA guidelines. Seventeen randomized control trials meeting the inclusion criteria were included for analysis. Interventions with type-2 diabetic SA showed significant improvements in HbA1c% (4/5 studies), fasting blood glucose (3/4 studies), and postprandial glucose (2/2 studies). Interventions with at-risk/prediabetic and non-diabetic SA showed a modest change in overall outcomes, with significant change reported for post-prandial insulin (3/4 studies), BMI and weight (2/4 studies), …

Prospective Investigation Of Insomnia Symptoms And Sleep Duration As Risk Factors For Stroke Incidence And All-Cause Mortality In U.S Adult, Wendemi Sawadogo

Theses and Dissertations

Background and Objectives: Stroke is the second leading cause of death in the world. In the United States, on average, someone has a stroke every 40 seconds and someone dies as a result of stroke every 3.5 minutes. Identifying modifiable risk factors of stroke is therefore a public health priority. The purpose of this study was to investigate the extent to which insomnia symptoms and sleep duration contribute to stroke incidence, all-cause mortality, and explore potential causal pathways.

Methods: The Health and Retirement Study (HRS) and the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were …

Changes In Physical Activity And Relationships To Submaximal Exercise Capacity And Cardiac Function During Breast Cancer Therapy, Moriah P. Bellissimo

Theses and Dissertations

Background: Breast cancer (BC) survivors are at high risk for heart failure due to curative cancer therapies. In non-cancer populations, physical activity is a first line treatment for preventing cardiovascular disease. This study examined whether more physical activity was associated with better submaximal exercise capacity and cardiac function during the first three months of cancer therapy.

Methods: Participants included 223 women with stage I-III BC before therapy and after three months of undergoing treatment and 126 controls. Leisure time physical activity was reported using the Godin Sheppard leisure time exercise questionnaire. Cardiac function was assessed by cardiac magnetic resonance, and …

The Influence Of Comorbid Gad On Er Utilization In Urban Youth With Asthma, David A. Karpe

Theses and Dissertations

Current literature indicates a strong association between asthma and the early onset of comorbid generalized anxiety disorder (GAD) in minors and their primary caregivers. Studies show that asthma prevalence increases with certain demographic factors, such as ethnicity, socioeconomic status, and housing quality. Evidence also suggests that GAD influences decision-making, especially when deciding to utilize emergency room (ER) services for asthma-related concerns. This study analyzed the effect of comorbid GAD on minors with asthma and ER utilization. The data were provided by an earlier Stress & Justice Study (S&J) baseline survey, an investigation aimed at understanding the impact of parental criminal …

Role Of P53 Deficient Clonogenic Endothelial Cells In The Pathogenesis Of Pulmonary Hypertension, Aneel Roy Bhagwani

Theses and Dissertations

Pulmonary Artery Hypertension (PAH) is a progressive disorder of the small vessels of the pulmonary vasculature. It is characterized by occlusive vascular remodeling leading to right heart failure and ultimately death. PAH pathogenesis involves a multifactorial etiology leading to formation of occlusive lesions in small (preacinary) pulmonary arteries. These lesions contain hyper-proliferative, apoptosis resistant endothelial cells (ECs), smooth muscle cells and fibroblasts. ECs play a major role in the development of PAH. These ECs in vascular lesions are primitive and express progenitor cell markers, including CD117 (c-kit).

We have isolated clonally expanded, c-kit+ ECs from the lungs of Green Fluorescent …

Cardiac Arrest And Global Ischemia Reperfusion Injury: Role Of Mitochondria And Cannabinoid Receptor 2 Signaling., Jennifer L. Bradley

Theses and Dissertations

We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial …

The Effects Of Interleukin-1Β On Cardiac Reserve And Exercise Capacity In The Mouse, Habeebah Z. Vohra

Theses and Dissertations

Heart failure (HF) is characterized by dyspnea, fatigue, and exercise intolerance. Clinical evidence points to increased interleukin-1β (IL-1β) activity in patients with HF, with an IL-1 blockade improving the exercise capacity in HF patients. In healthy mice, recombinant-mouse IL-1β (rmIL-1β) induces acute systolic dysfunction, peaking 4 hours after administration. However, the direct effects of rmIL-1β on exercise capacity are unknown. We hypothesized that rmIL-1β diminishes the exercise capacity in the mouse. Adult mice were trained to run on a treadmill and exercise capacity was assessed before, 4 hours, and 96 hours after intraperitoneal administration of rmIL-1β (3 μg/kg) or vehicle …

Impact Of Physical Activity And Cardiorespiratory Fitness On Vascular Homeostasis In Premenopausal Women Consuming A Westernized High-Fat Meal, Lauren N. Pedersen

Theses and Dissertations

A large percentage of adults in industrialized nations consume a Westernized dietary pattern, which contributes to fasting dyslipidemia and increased risk for atherosclerotic cardiovascular disease. Evidence suggests that a single Westernized meal containing high saturated fat may induce alterations in blood lipids as well as disturb multiple factors regulating peripheral vascular homeostasis, including innate immune cell function, oxidative stress, and vascular function. Conversely, participation in acute and chronic exercise may beneficially impact an individual’s postprandial response. Therefore, this dissertation contains three manuscripts seeking to describe how acute exercise, cardiorespiratory fitness, and physical activity level impact the lipemic and vascular homeostatic …

The Effects Of An Inflammasome Inhibitor Olt1177 On The Development Of Ischemic Heart Failure, Joseph S. Aliaga

Theses and Dissertations

Thesis Abstract

THE EFFECTS OF AN INFLAMMASOME INHIBITOR OLT1177 ON THE DEVELOPMENT OF ISCHEMIC HEART FAILURE

By Joseph S. Aliaga, BS

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2020

Background: Evidence suggests that prolonged and enhanced pro-inflammatory signaling, modulated by the NLRP3 inflammasome, plays a crucial role in the pathophysiology of several different types of cardiovascular diseases such as acute myocardial infarction (AMI), adverse ventricular remodeling, and heart failure (HF). Consequently, we hypothesize that attenuating the enhanced inflammatory response using a pharmacological NLRP3 …

The Role Of Interleukin-18 In Myocardial Ischemia/Reperfusion, Yogesh Dhakal

Theses and Dissertations

Acute Myocardial Infarction (AMI) is one of the leading causes of morbidity for cardiovascular diseases (CVDs) in the western world. While mortality rates for AMI has reduced in the last 20 years due to advancements in clinical interventions, patients who have an AMI are significantly more likely to develop heart failure (HF) in the following years. Reperfusion of the ischemic tissue is a necessary procedure to restore blood delivery to cardiomyocytes, minimize myocardial dysfunction, and reduce infarct size. Still, the step of reperfusion itself induces myocardial damage in a phenomenon known as reperfusion injury. Considering that the degree of myocardial …

Accounting For The Uncertainty Due To Chemicals Below The Detection Limit In Mixture Analysis, Paul M. Hargarten

Theses and Dissertations

Humans are exposed to multiple chemicals every day. Epidemiological studies have shown that chemical mixtures are associated with cancers, allergies, neurodevelopmental disorders, and other adverse health effects. To assess these associations, investigators are increasingly using chemical mixture approaches like weighted quantile sum (WQS) regression. In these studies, the research objectives are to determine whether a mixture of correlated chemicals is associated with an adverse health outcome and to identify the important chemicals. However, as experimental equipment measures each exposure to a chemical-specific detection limit, the exposures are unknown between zero and the detection limit. Indeed, the number of exposures below …

Process Factors Affecting Reperfusion Time In Patients Presenting With St-Segment Elevation Myocardial Infarction (Stemi), Richard R. Wall

Theses and Dissertations

Abstract PROCESS FACTORS AFFECTING REPERFUSION TIME IN PATIENTS

PRESENTING WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) By Richard R. Wall MSRS, RT(R)(CT)(CI), RCIS

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2020.

Dissertation Chair: Jeffrey S. Legg Ph.D. Associate Professor and Chair, Department of Radiation Sciences

An ST-segment myocardial infarction (STEMI) occurs when the blood flow to the myocardium is suddenly and completely blocked causing the myocardium to become ischemic. A STEMI is a life-threatening condition that necessitates emergent medical treatment. Research has shown that longer …

Incidence And Predictor Variables Of Pressure Injuries In Patients Undergoing Ventricular Assist Device And Total Artificial Heart Surgeries: An Eight-Year Retrospective Review, Christopher T. Brindle

Theses and Dissertations

BACKGROUND

Cardiac surgery patients have some of the highest reported incidence and prevalence of pressure injuries (PI). A growing subset of cardiac surgery include patients with end-stage heart failure who undergo ventricular assist device (VAD) or total artificial heart (TAH) surgery. The risk of PI and their natural history of development in this population are unknown and the specific risk factors for PI development remain unexplored.

OBJECTIVES

To perform a systematic review of the literature to identify the incidence and risk factors of PI development in patients undergoing VAD-TAH surgery and thereby inform study design and variables in an eight-year …

Therapeutic Targeting Of Relaxin Signaling In Ischemic Heart Disease, Siva Teja Vk Devarakonda

Theses and Dissertations

Ischemic heart disease is characterized by reduced perfusion of oxygenated blood to the myocardium, potentially resulting in infarction upon occlusion of coronary arteries. While prompt reperfusion and advances in in-hospital care have led to a decline in short term mortality, sustained damage to the ventricle, along with reperfusion injury, can lead to progressive deterioration in cardiac function. Limiting the extent of this initial ischemia-reperfusion injury and combating the course of adverse remodeling remains the scope of several preclinical studies geared towards improving cardiac health after MI. To this, relaxin-2 – the peptide hormone that regulates maternal hemodynamic function during pregnancy …

Examination Of Strain-Dependent Differences In S. Sanguinis Virulence And Growth, Shannon Baker

Theses and Dissertations

Streptococcus sanguinis, an abundant and benign inhabitant of the oral cavity, is an important etiologic agent of infective endocarditis, particularly in people with pre-disposing cardiac valvular damage. Although commonly isolated from patients with IE, little is known about the factors that make any particular S. sanguinis isolate more virulent than another or, indeed, whether significant differences in virulence exist among isolates. To investigate the virulence of multiple isolates, a variation of the Bar-seq (barcode sequencing) method was employed. A conserved chromosomal site was identified for subsequent insertion of a barcode identifier, unique for each strain. Barcode insertion did not …

Diuretic And Natriuretic Activity Of Faah Inhibition In The Renal Medulla: A Proposed Role Of Palmitoylethanolamide And Its Regulation By Renal Medullary Interstitial Cells, Sara Dempsey

Theses and Dissertations

Hypertension is a critical public health issue worldwide, and in the United States, it is the leading cause of heart disease, stroke, and kidney failure, contributing to more than 1,100 deaths per day. It is proposed that the renal medulla combats increased blood pressure by releasing a neutral lipid from the lipid droplets of medullary interstitial cells, termed medullipin, which induces diuresis- natriuresis and vasodepression. The renal medulla is enriched with fatty acid lipid ethanolamides including the endocannabinoid anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), along with their primary hydrolyzing enzyme fatty acid amide hydrolase (FAAH). Our lab is investigating …

Counterregulatory Effects Of Ptx3 On Inflammation And Cellular Aging, Aaron L. Slusher

Theses and Dissertations

Pentraxin 3 (PTX3) is a vital regulator of innate immune function that has been shown to counterregulate pro-inflammatory signaling and protect against the development of cardiovascular disease (CVD). Less is known about how PTX3 may mitigate against CVD risk by regulating the pro-inflammatory response at the cellular level. Therefore, this dissertation details four manuscripts which aimed to examine the capacity of PTX3 to regulate the innate immune response of peripheral blood mononuclear cells (PBMCs) isolated from healthy adults. Manuscript 1 examined the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of isolated PBMCs with the pro-inflammatory …

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …

5-Ht2b Receptor-Mediated Cardiac Valvulopathy, Pallavi Nistala

Theses and Dissertations

5-HT_2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens …

Effects Of The Na-Cl Co-Transporter (Ncc) In Western Diet Induced Metabolic And Cardiac Dysfunction, Zachary S. Cutter

Theses and Dissertations

Interleukin-18 (IL-18) is a pro-inflammatory cytokine known to be involved in maintaining metabolic homeostasis; however, also capable of inducing cardiac dysfunction. Additionally, IL-18, has been shown to bind to a novel receptor, the Na-Cl Co-transporter (NCC). We hypothesized that NCC mediates IL-18 metabolic and cardiac signaling in mice. Using male C57BL/6J mice, we compared the metabolic and cardiac function changes after at least 8 weeks of high-saturated fat high sugar diet (Western Diet) in NCC knockout (NCCKO), IL-18 knockout (IL-18KO), and wild-type mice. We show that NCCKO mice have significantly increased body weight gain from baseline, no difference in fasting …

Contribution Of Asc-Inflammasome To Vascular Endothelial Dysfunction: Role Of Rna Receptor Rig-I, Ashley Pitzer

Theses and Dissertations

Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase and recently identified as a cytosolic RNA receptor in mammalian cells. The role of RIG-I in the regulation of vascular function under physiological and pathological conditions is unknown. Recent studies have shown that the inflammasome serves as a crucial initiator of cytokine-mediated inflammation mediating the pathogenesis of cardiovascular disease. The present study tested whether RIG-I activation triggers inflammasome formation and subsequent cytokine-mediated inflammation in the endothelium of mice coronary arteries. Using both genetic and pharmacological interventions of the RIG-I inflammasome, we first characterized whether specific activation of RIG-I via 3pRNA transfection …

Contribution Of A Class Ii Ribonucleotide Reductase To The Manganese Dependence Of Streptococcus Sanguinis, John L. Smith

Theses and Dissertations

Manganese-deficient Streptococcus sanguinis mutants exhibit a dramatic decrease in virulence for infective endocarditis and in aerobic growth in manganese-limited media. Loss of activity of a manganese-dependent, oxygen-dependent ribonucleotide reductase (RNR) could explain the decrease in virulence. When the genes encoding this RNR are deleted, there is no growth of the mutant in aerobic broth culture or in an animal model. Testing the contribution of the aerobic RNR to the phenotype of a manganese transporter mutant, a heterologous class II RNR from Lactobacillus leichmannii called NrdJ that requires B₁₂ rather than manganese as a cofactor was previously introduced into an …

Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash

Theses and Dissertations

The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Exploring The Role Of Intersectionality On Cardiovascular Disease Risk In Sexual Minorities, Leia Harper

Theses and Dissertations

Background: Previous research has shown that sexual minority individuals (SM) are twice as likely to smoke, twice as likely to be overweight or obese, and less likely to be physically active than heterosexual persons; all of which place SMs at an increased risk for cardiovascular disease (CVD). While information on CVD risk by race/ethnicity and socioeconomic status is well documented, there is scant literature examining race, gender, and the potential CVD risk in SMs. The purpose of this study was to examine CVD risk in sexual minorities.

Method: The current study used data from the National Longitudinal Study of Adolescent …