Cardiovascular Diseases Commons^™

Evaluating The Effect Of Skipping Ticagrelor Doses And Need For Bolus Doses Upon Treatment Resumption Through Population Pk/Pd Simulation, Hiroyoshi Matsui, Le Thien Truc Pham, Eyob D. Adane

ONU Student Research Colloquium

Ticagrelor (Brilinta (R)) is the first reversibly binding oral P2Y12 receptor antagonist. It is used, mostly in combination with aspirin, in patients with acute coronary syndromes to reduce thrombosis. The manufacturer of ticagrelor recommends discontinuing it at least 5 days before any surgery when possible. While the effect of dose interruptions on the risk of thrombosis is not directly studied, it is important to understand the impact of skipping doses on ticagrelor's PK/PD profile for clinical-decision making. The objectives of the current study were to simulate the impact of therapy interruption on the PK/PD of ticagrelor and examine the need …

Green Tea Supplementation: An Effective Lifestyle Modification For Cholesterol Management, Samuel J. Nemati

MSN Capstone Projects

Hypercholesterolemia is an insidious disease and the leading factor to the deadliest killer in the United States – cardiovascular disease (Centers for Disease Control and Prevention, 2023a). Over 85 million American adults suffer from elevated cholesterol, and treatment can prove challenging and may require multiple modalities outside just pharmaceutical intervention – such as dietary and other lifestyle changes (Centers for Disease Control and Prevention, 2023b; Goldman, 2023). Green tea – among the most common teas consumed worldwide – exerts a uniquely antihyperlipidemic and cardioprotective effect that suggests its consideration as a potentially-viable nonpharmacological option for hypercholesterolemia (Harvard Health Publishing, 2012; …

“Cost-Effective Markers To Identify Metabolically Healthy/Unhealthy Individuals And Their Future Risk For Cardiovascular Disorders”, Shobha C Ramachandra, Akila Prashant, Akshitha Shivanna, Ananth Koushik Bhujanga, Syeda Meherunnisa, Prashant Vishwanath

International Journal of Health and Allied Sciences

Background: With the rising prevalence of metabolically healthy obese, it becomes essential to identify markers to differentiate them from metabolically unhealthy obese and their future risk for cardiovascular disorders (CVD). The study aims to identify suitable markers for risk stratification of metabolically healthy/unhealthy individuals and their risk for CVD. Method: Total 84 individuals aged 18-60 years of age without any comorbidities were enrolled. Their demographic details along with anthropometric measurements were noted. The biochemical parameters like fasting glucose, insulin, lipid profile, and serum adipokines were estimated. Insulin resistance (IR) markers and atherogenic indices were calculated. The data were analyzed on …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Is There A Role For Plant-Based “Meat” In Cardiovascular Disease Prevention?, Aziza Jadallah, Usmaan Al-Shehab, Adam Friedman

Rowan-Virtua Research Day

Diet is an established risk factor for cardiovascular disease. The American Heart Association recommends following a whole-food, minimally processed diet emphasizing fruit and vegetables to reduce cardiovascular mortality. Recently, processed plant-based meat substitutes, such as Beyond Meat® and Impossible™ foods have become easily accessible to consumers and are advertised as a healthful addition to a plant-based diet. However, these products are highly processed and contain high amounts of saturated fat and sodium. The purpose of this research is to investigate the effect of processed plant-based meat diets on adverse cardiovascular events compared to animal-based meat diets and minimally processed healthful …

The Impact Of High-Intensity Interval Training On Vascular Function In Adults: A Systematic Review And Meta-Analysis, Mousa Khalafi, Mohammad Hossein Sakhaei, Fatemeh Kazeminasab, Michael E. Symonds, Sara K. Rosenkranz

Kinesiology and Nutrition Sciences Faculty Publications

Aim: We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) compared with moderateintensity continuous training (MICT) or with no exercise (CON) on vascular function in adults who were free of cardiometabolic diseases and those with cardiometabolic diseases.

Methods: A search across three electronic databases including Scopus, PubMed, and Web of Science was conducted through February 2022 to identify the randomized trials evaluating HIIT vs. MICT and/or CON on vascular function as measured using brachial artery flow-mediated dilation (FMD) in adults. Separate analyses were conducted for HIIT vs. MICT and/or CON to calculate weighted …

The Associations Of Chronic Stress, Social Support, Health Behaviors And Metabolic Syndrome Among Hispanic Women, Edna Esquer

Dissertations

The Associations of Chronic Stress, Social Support, Health Behaviors and Metabolic Syndrome Among Hispanic Women

Background: Metabolic syndrome (MetS) prevalence is 25% among Mexican American women 30 – 49 years of age, compared to 22% among non-Hispanic Whites in the United States. Little is known about the additional contributions of chronic stress, social support and health behaviors to the development of MetS among this population.

Purpose: Describe the associations between chronic stress, social support, and health behaviors and the presence of MetS in Hispanic women living in an underserved community.

Methods: A retrospective cohort study design. The Adult Treatment Panel …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis that …

Effectiveness Of Individual Nutrition Education Compared To Group Education, In Improving Anthropometric And Biochemical Indices Among Hypertensive Adults With Excessive Body Weight: A Randomized Controlled Trial, Danuta Gajewska, Alicja Kucharska, Marcin Kozak, Shahla M. Wunderlich, Joanna Niegowska

Department of Nutrition and Food Studies Scholarship and Creative Works

Objective: The study aims to compare the effectiveness of individual and group nutrition education methods in improving key anthropometric and biochemical markers in drug-treated, overweight-obese hypertensive adults. Methods: The randomized trial included 170 patients with pharmacologically well-controlled primary hypertension and body mass index (BMI) ≥ 25 kg/m². For six months, the patients received six sessions, either one-to-one individual nutrition education (IE, n = 89) or group education (GE, n= 81), developed by dietitians. Anthropometric measurements, body composition, and fasting measures of biochemical parameters were obtained at baseline and after six months of intervention. Results: 150 patients completed the …

The Acute Effect Of Water Intake On Glucose Regulation In Low Drinkers, Adam David Seal

Graduate Theses and Dissertations

Previous evidence suggests the hormone arginine vasopressin (AVP) may be a modifiable factor contributing to hyperglycemia. Significant differences in urine concentration and copeptin, a marker for AVP, have been observed between low and high water drinkers. Purpose: The purpose was to investigate the acute effect of adequate water intake on glucose regulation in low drinkers. Methods: 7 healthy (5 males, 2 female) low drinkers were recruited using a water frequency questionnaire (WFQ), spot and 24-h urine sample (age 43±6 y, BMI 30.9±3, WFQ volume 823±403 mL∙d-1, 24 h Uosm 961±105 mmol∙kg-1, copeptin 8.17±3.05 pmol∙L-1). During two experimental protocols, participants remained …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Joseph I Shapiro MD

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Komal Sodhi

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

The Effects Of Habitual Protein Consumption On Vasodilation In Young Adults, Natalie O'Neal, Jordan Rezac

Health, Human Performance and Recreation Undergraduate Honors Theses

Introduction: Blood pressure is a critical indicator for a number of health risks and conditions, such as hypertension (high blood pressure), heart failure, and stroke. Decreasing blood pressure occurs by vasodilation (relaxation) of blood vessels. The consumption of high amounts of protein is hypothesized to have a correlation with the vasodilation of vessels, thus creating a decrease in blood pressure. Purpose: The purpose of this study was to relate blood vessel diameter to habitual protein consumption. Our findings have the power to make individuals more aware of the effect their habitual protein intake can have on cardiovascular health. Methods: This …

The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou

Electronic Theses and Dissertations

The goal of this study is to investigate the effects of wild blueberry fractions (Anthocyanins and Phenolic acids) on vascular function and physiology. More specifically the potential effects of the above fractions and their combination in physiological concentrations on endothelial cell migration, angiogenesis, gene expression and proteins synthesis of markers related to the above processes. The objectives are to study whether anthocyanins, phenolic acids and their combinations (ACNs:PAs) affect: a) cell proliferation, b) speed of endothelial cell migration, c) angiogenesis, d) gene expression of genes critical for cell migration and angiogenesis such as RAC1, RHOA, AKT1, eNOS and VEGF and …

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, …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

Cpt1a Methylation Is Associated With Plasma Adiponectin, S. Aslibekyan, A. N. Do, H. Xu, S. Li, M. R. Irvin, D Zhi, H. K. Tiwari, D. M. Absher, A. R. Shuldiner, T. Zhang, W. Chen, K. Tanner, C. Hong, B. D. Mitchell, G. Berenson, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background and Aims—Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood.

Methods and Results—We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n= 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Biochemistry and Microbiology

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough

Kevin M Rice

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

Elsa I. Mangiarua

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …

Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough

Ravi K. Arvapalli

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

Eric Blough

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …

Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough

Eric Blough

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

Silvestre P. Cansino

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

Paulette S. Wehner

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …

Metabolic Regulation Of Mtor Activation And Endoplasmic Reticulum Stress In The Heart, Shiraj Sen

Dissertations & Theses (Open Access)

When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac …

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 …

Elucidating The Genetic Determinants Of The Archetypal Complex Disease Hypertriglyceridemia, Christopher T. Johansen

Electronic Thesis and Dissertation Repository

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Canada. Among non-traditional risk factors, plasma triglyceride (TG) concentration is re-emerging as a significant risk factor. Patients with hypertriglyceridemia (HTG) – an archetypal complex phenotype defined by fasting plasma TG concentration >95^th percentile – thus have significantly increased CVD risk, compounded by associated co-morbidities such as obesity, metabolic syndrome and type 2 diabetes. However, the molecular pathways contributing to HTG susceptibility are incompletely defined. A better understanding of the genetic determinants that underlie the phenotypic spectrum of plasma TG and HTG susceptibility is necessary to identify novel …

Acetaminophen Protects Against Iron-Induced Cardiac Damage In Gerbils, Ernest M. Walker Jr., Christopher P. Epling, Cordel Parris, Silvestre Cansino, Protip Ghosh, Devashish H. Desai, Ryan G. Morrison, Gary L. Wright, Paulette Wehner, Elsa I. Mangiarua, Sandra M. Walker, Eric R. Blough

MIIR Faculty Research

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and …