Medicine and Health Sciences Commons^™

Mechanisms Underlying Enhanced Bone Marrow Adipogenesis In Diabetes, Jina J.Y. Kum

Electronic Thesis and Dissertation Repository

Morbidity and mortality associated with diabetes are due to secondary vascular complications that include both micro- and macro-vascular organ dysfunctions. Our recent studies show that vascular dysfunction and inadequate vessel repair in diabetes may potentially be due to impaired vasculogenesis (de novo vessel formation). Specifically, we have shown that diabetes enhances adipogenesis in the bone marrow and reduces the number of marrow-resident vascular regenerative stem cells. In this study, I have determined the mechanisms of deleterious bone marrow adipogenesis, which may alter the cellular composition of the marrow and lead to the depletion of vascular regenerative stem cells.

My …

Endothelial Cell-Specific Loss Of Breast Cancer Susceptibility Gene 2 Exacerbates Atherosclerosis, David C.R. Michels

Electronic Thesis and Dissertation Repository

Despite mounting concern over the increased risk of cardiovascular disease in breast cancer patients, studies evaluating the common genetic/molecular link between these diseases are limited. Mutations in the breast cancer susceptibility genes (BRCA1&2) predispose carriers to breast and ovarian cancers due to compromised DNA damage repair capacity leading to DNA damage accumulation; in cancer cells, and in other cell-types including endothelial cells, causing atherosclerotic hallmarks of endothelial dysfunction/apoptosis. We present a new understanding of BRCA2’s protective functionality in the setting of atherosclerosis. Studies have thus far demonstrated that while loss of endothelial BRCA2 in mice does not affect a molecular …

Effects Of Ergothioneine On Endothelial Cell And Macrophage Characteristics, And Markers Of Atherosclerosis Risk Under High Lipid Conditions, Daniel Lam-Sidun

Electronic Thesis and Dissertation Repository

Ergothioneine (EGT) is an antioxidant and potential anti-inflammatory molecule that may have protective effects against the lipid-induced oxidative stress and inflammation that occurs in the vasculature of individuals with obesity and metabolic syndrome. This thesis addresses the hypothesis that EGT supplementation decreases endothelial cell dysfunction and macrophage inflammatory characteristics under high lipid conditions, and markers of atherosclerotic risk in diet-induced obese mice. Results showed that EGT did not influence endothelial tube formation or stability but reduced nitric oxide production in endothelial cells. Moreover, EGT decreased the production of reactive oxygen species, and potentially nitric oxide, by macrophages. In diet-induced obese …

Genetic Approaches For The Study Of Complex Human Diseases, Julieta Lazarte

Electronic Thesis and Dissertation Repository

The field of human genetics has evolved from its initial narrow focus on single-gene Mendelian disorders, which largely affect children, to our current understanding that for most diseases there is continuum of rare to common variants which can exert a range of phenotypic effects. Despite advances in sequencing capabilities and our overall understanding of diseases, there remains a large proportion of heritability unexplained. Through the use of next-generation sequencing technologies and DNA microarray, I have explored a spectrum of genetic variations from rare, single and structural variants to common variants in individuals with i) “lone” atrial fibrillation; ii) familial hypercholesterolemia; …

Measuring The Impact Of Atrial Fibrillation On Patients, Justine Chang

Electronic Thesis and Dissertation Repository

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Patients experience the effects of AF from early symptom onset to treatment and beyond. A previous qualitative study found AF to substantially affect patients’ emotional wellbeing, social relationships, employment, and finances. Existing quality of life questionnaires do not adequately assess the AF impact. In this thesis, a new patient-reported questionnaire was developed to measure the impact of AF as experienced by patients. An exploratory factor analysis was conducted on the new questionnaire, revealing five domains: “Affect”, “Social Support”, “Major Life Events”, “Financial Impact”, and “Diagnostic Experience”. Age, marital status, educational …

Novel Imaging Tools Reveal The Dynamics Of The Myocardial Growth Hormone Secretagogue Receptor In Heart Disease And Heart Failure, Rebecca Sullivan

Electronic Thesis and Dissertation Repository

Heart disease (HD) is the leading cause of mortality worldwide. Currently, diagnosis is based on clinical features, imaging, and circulating cardiac biomarkers. Cardiac imaging technologies, such as echocardiography and cardiac magnetic resonance imaging (cMRI), enable the non-invasive detection of changes in heart function. Although these modalities can detect changes in structure and anatomy, it is usually at later stages, where prevention may not be possible. In conjunction with imaging, circulating biomarkers of heart failure (HF), notably B-type natriuretic peptide (BNP) and cardiac troponin I and T, can be detected with increased levels in the blood. These biomarkers are associated with …