Investigation Into Sepsis-associated Alterations Of The Arterial Endothelium As A Priming Event For Atherogenesis

Abstract

Sepsis is the life-threatening response to infection characterized by a dysregulated host response. Survivors of sepsis experience an increased risk of cardiovascular complications. While the underlying pathophysiology of this observation is multifactorial, endothelial Sepsis is the life-threatening response to infection characterized by a dysregulated host response. Survivors of sepsis experience an increased risk of cardiovascular complications. While the underlying pathophysiology of this observation is multifactorial, endothelial dysfunction in sepsis is thought to be a major contributor to atherogenesis. This project aimed to examine adhesion molecule expression in the aortic sinus of wild-type mice fed a high-fat diet. We hypothesized that sepsis upregulates adhesion molecule expression on the arterial endothelium in high-fat-diet fed mice. Five-to-seven-week-old C57BL/6J mice were fed either a high-fat diet (60% butterfat) or a low-fat diet (21% butterfat) for 16 weeks. Mice that were only fed a chow diet until 16-17 weeks of age (naïve mice) served as a separate control group. Sepsis was induced through an intraperitoneal injection of fecal slurry prepared from Sprague Dawley rat feces. Control mice received an equivalent volume of a 5% dextrose solution. The aortic sinus endothelium was evaluated using hematoxylin and eosin staining, and immunofluorescent staining for von Willebrand factor (VWF) and Vascular Cell Adhesion Molecule 1 (VCAM-1). There is no difference between septic and non-septic groups, regardless of diet, considering mean fluorescent intensity of VCAM-1 and VWF. Irrespective of diet, there was no difference in the percentage of endothelium stained with VCAM-1 and VWF between septic and non-septic mice. The percentage of endothelium stained with VWF was significantly different in LFD-CTL, LFD-FIP, and HFD-FIP mice compared to naïve mice. This study reports for the first time, the effects of sepsis in mice fed a high-fat diet. While there were no significant changes in septic mice from the non-septic control mice, this study reveals the importance of choosing an appropriate control diet. Our results suggest that another trigger may be required for a pro-atherogenic state post-sepsis, or a longer time post-sepsis should be evaluated.