Circulatory and Respiratory Physiology Commons^™

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

UT GSBS Dissertations and Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury that elicits occlusive thrombi ...

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

University of Western Ontario - Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and ...

Improving Cardiac Repair By Stem Cell Factor Post-Myocardial Infarction, Fuli Xiang

University of Western Ontario - Electronic Thesis and Dissertation Repository

Myocardial infarction (MI) occurs due to the complete occlusion of a coronary artery and is a leading cause of death, and a huge social and economic burden worldwide. Despite advances in treatment, patients still have a poor prognosis and there is a pressing need for strategies to improve cardiac repair post-MI. Stem cell factor (SCF), expressed by many cells and tissues including the myocardium, binds to its receptor, c-kit, and regulates the activity of c-kit-expressing cells. SCF has two isoforms: a soluble (S-SCF), and a membrane-associated isoform (M-SCF). M-SCF is more potent in supporting cell adhesion and survival. To ...

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms In Angiotensin Ii-Infused Mice, Xiaojie Xie, Hong Lu, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum concentrations ...

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred ...

Modeling Lung Structure In Rodents, William B. Counter

Open Access Dissertations and Theses

Pre-clinical imaging has provided pulmonary researchers with a number of valuable tools for studying both the lung and lung disease. A greater understanding of the structure/function relationships within the rodent lung would help to bridge the gap between functional images of the lung and its underlying anatomy.

The objectives of this work were to visualize and measure the components of rodent lung anatomy. Contrast-enhanced microCT images were used to visualize the airways and major blood vessels from both the Sprague-Dawley rat and the BALB/c mouse. These observations and measurements were used in the development of a pulmonary lung ...

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic ...

Lung-Homing Of Endothelial Progenitor Cells And Angiogenesis In Asthma: Role Of Eosinophils, Nirooya Sivapalan

Open Access Dissertations and Theses

Asthma involves a systemic element that includes the mobilization and lung-accumulation of bone marrow-derived endothelial progenitor cells (EPC). This traffic may be driven by the stromal cell derived factor-1α (SDF-1α)/CXCR4 axis, where SDF1-α is a potent progenitor cell chemoattractant.

Interfering with EPC lung-accumulation by administering AMD3100, a CXCR4 antagonist, was previously shown to be associated with the modulation of airway angiogenesis and airway hyperresponsiveness. However, since eosinophils express CXCR4, it is unknown whether AMD3100 acted directly on EPC or indirectly through its anti-inflammatory effects on eosinophils.

We investigated the role that eosinophilic inflammation plays in the lung-homing of EPCs ...

The Role Of Neutrophils In Severe Asthma, Afia Aziz-Ur-Rehman

Open Access Dissertations and Theses

Various studies have shown an association between neutrophilic airway inflammation and severe asthma, but have failed to establish a causal relationship. In these studies airway neutrophilia could be due to high steroid doses, an airway infection, an epiphenomenon of severe asthma or a combination of these. We have examined the role of neutrophils in severe asthma in patients on optimum steroid doses with controlled eosinophilic airway inflammation and chemotactic activity of IL-17 as one potential mechanism of neutrophil recruitment to the airway.

We examined the number, viability and activity of neutrophils in blood and sputum of three groups of asthma ...