The epidemic of obesity-related metabolic and cardiovascular diseases is linked to elevated fatty acids (FA). Epidemiological data argue that trans FA contribute to the development and progression of these disease processes. Previous work suggests the similarity in structure between saturated and trans FA may stimulate inflammation through trans FA interactions with toll-like receptor 4 (TLR4). To evaluate the impact of trans FA on cardiovascular health, the response of endothelial cells to trans FA was evaluated. Specifically, responses to the 18-carbon trans FA elaidic acid (EA) were compared to the same length cis FA oleic acid (OA). Endothelial cells were exposed to FA treatments for up to 48 hours and protein samples collected at specific times (1.5, 3, 6, 12, 24, and 48 hr). The expression of connexin43 (Cx43) was evaluated using Western blot analysis as a measure of their health (increasing in unhealthy endothelial cells). Lipopolysaccharide (LPS; 10 μg/mL), a TLR4 agonist, stimulated an increase in endothelial cell Cx43 expression at 12 hours. As the endothelial cells responded to a TLR4 agonist, they were then exposed to OA (30 μM), which decreased the expression of Cx43 at 3, 12, and 24 hours. In contrast, EA (30 μM) increased Cx43 expression at 12 hours. These results suggest that trans FA alter Cx43 expression in a similar pathway as LPS in endothelial cells (likely TLR4 signaling), whereas OA decreased Cx43, likely through a different mechanism
