PhD Defense by Christa Caesar

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Christa Caesar

BME PhD Defense Presentation

January 6th, 2016

10am

Division of Cardiology Conference Room (WMB 315)

Woodruff Memorial Building, Emory University

 

Advisor:

W. Robert Taylor, MD, PhD

 

Thesis Committee Members:

Hanjoong Jo, PhD

Roy Sutliff, PhD

Rudolph L. Gleason, PhD

Michael Davis, PhD

Title:

Osteopontin as a Mediator of Vascular Inflammation and Biomechanics

Abstract:

Hypertension has an impact on nearly 70 million Americans and 1 billion individuals worldwide currently. It is one of the most readily identifiable risk factors for myocardial infarction (MI), stroke, aortic aneurysms, dissections, and peripheral vascular disease. Studies have shown that the aorta experiences elevated mechanical strain in the setting of hypertension, which leads to vascular inflammation, and a plethora of additional cardiovascular complications. However, many of the underlying molecular mechanisms modulating this strain-dependent inflammation of the aorta are still largely unexplored. Therefore, the overall goal of this work was to analyze the specific role and regulation of the protein, osteopontin (OPN) in the aorta, in the context of hypertension. OPN has recently emerged as an important pro-inflammatory protein and mediator of tissue remodeling.

We first evaluated the expression and regulation of OPN in response to mechanical strain using an in-vitro system, where aortic smooth muscle cells were cultured and cyclically strained on flexible membrane culture plates. Next, we evaluated the expression of OPN and its hydrogen peroxide-dependent regulation in the aorta, using two in-vivomodels of murine hypertension. Finally, we explored the contribution of OPN to the mechanical properties of the aorta under healthy and hypertensive conditions. We have found that OPN is in fact up-regulated with hypertension, and plays an important role in mediating inflammation and remodeling of the aorta. Overall these results deepen our understanding of vascular inflammation, and could have important implications in the design of future therapies and strategies aimed against the consequences of hypertension.           

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