Year of Publication

2013

Degree Name

Master of Science in Medical Sciences (MSMS)

Document Type

Master's Thesis

College

Medicine

Department

Toxicology

First Advisor

Dr. Alan Daugherty

Abstract

A previous thoracic aortic aneurysm time course study from our laboratory determined that ascending aortic dilation was significantly increased by day 5, and reached a plateau by day 28 of angiotensin II (AngII) infusion. We also found that mice had hemorrhage localized to the ascending aortas by day 5 of AngII infusion. The purpose of these studies was to provide mechanistic insight into the development of AngII-induced ascending aortic hemorrhage.

Male C57BL/6 mice fed normal diet were subcutaneously infused with either AngII (1000 ng/kg/min) or saline for 5 days. To examine cellular heterogeneity, hemorrhaged ascending aortas were collected and sectioned serially for histological staining and immunostaining. I was unable to identify an entry point for blood into the media of the aortic root and ascending aorta. However, I found incomplete intimo-medial dissection near the hemorrhaged regions that may potentially be contiguous with the blood. To investigate infiltration of immune cells during AngII infusion, immunohistochemistry of hemorrhaged ascending aortas was performed. The numbers of macrophages and neutrophils in AngII-infused aortas were increased in both medial and adventitial areas when compared with saline-infused aortas.

Therefore, infiltration of immune cells at the point of dissection is associated with aortic hemorrhage during AngII infusion.

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