Examining innovative methodological approaches to assess the human vascular system

Abstract

There are a multitude of approaches to assess the vascular system. MRI and ultrasound as well as blood assays have been used in experimental and clinical environments for decades. Coupled with innovative approaches to elicit meaningful and precise responses and applying them to novel populations make these tools even more powerful. This dissertation aimed to examine some of these newer, innovative approaches to examine vascular function in the human body. BOLD MRI coupled with sequential gas delivery has been applied to study and diagnose vascular pathologies, but the methodology of sequential gas delivery stimuli had never been tested within and between days using a ramp protocol. Ultrasound has been used in maternal-fetal echocardiography for decades, but very few studies have been conducted to examine the structure and function of the fetal abdominal aorta, especially under diabetic conditions. Innovative molecular techniques have been established to measure endothelial cell function in vitro which allows a better understanding of vascular consequences related to e-cig use. This dissertation has provided insight into these vascular methodologies and conditions.First, the within- and between-day reproducibility was conducted on a ramping protocol using precise sequential gas delivery within an MRI scanner using BOLD imaging techniques. This study observed that precisely controlling the amount of systemic carbon dioxide in a linear fashion spanning the physiological range is reproducible and tolerated. The implications of this study are twofold: 1) It can guide research design to uncover subtle vascular impairments and 2) Acute as well as longitudinal interventional and observational CVR experiments can be implemented more confidently. The second study presented in this dissertation explored the feasibility of using conventional echocardiography coupled with wall tracking software to image, measure, and compare the vascular structure and function of the fetal abdominal aorta. This study not only showed that imaging and measuring the fetal abdominal aorta is feasible within normal mothers, but also in diabetic mothers. Additionally, we observed measurable differences between these fetal environments. It gives insight into how in utero conditions may impact elastic development and, thus, predispose offspring to future cardiovascular consequences. The impacts include guiding clinicians to modify prenatal medical and lifestyle interventions and, ultimately, reduce the burden of cardiovascular disease later in life. Finally, the last study described in this dissertation used microvesicles isolated from e-cig user’s plasma to treat endothelial cells in vitro. We, then, analyzed the resulting protein expressions of inflammation precursors and eNOS which are known to influence endothelial function. The main observations were that microvesicles from e-cig users mediated endothelial dysfunction by reducing NO production of endothelial cells by ~20% compared to matched controls. In addition, this process was mediated by NF-κB activation. The conclusion drawn from this study is that microvesicles derived from e-cig use induce a pro-inflammatory dysfunctional endothelial phenotype as a result. The implications of this study were that the use of e-cigarettes is not benign and may increase the risk of future vascular consequences. In conclusion, this dissertation examined innovative methodological approaches to assess the human vascular system. First, it showed the reproducibility of an emerging method to measure cerebrovascular function, secondly it established the feasibility of assessing fetal vascular structure and function, and finally it elucidated the effects of e-cig use on endothelial function. It has shed light on just some of what is experimentally possible in relation to the vascular system and the impacts of innovation.