Trafficking of Endogenous Smooth Muscle Cell Cholesterol
A Role for Serum Amyloid A and Interleukin-1ß
Objective—Intracellular cholesterol distribution impacts cell function; however, processes influencing endogenous cholesterol trafficking remain largely unknown. Atherosclerosis is associated with vascular inflammation and these studies address the role of inflammatory mediators on smooth muscle cell cholesterol trafficking.
Methods and Results—Interestingly, in the absence of an exogenous cholesterol source, serum amyloid A (SAA) increased [14C] oleic acid incorporation into cholesteryl ester in rat smooth muscle cells, suggesting endogenous cholesterol trafficking to the endoplasmic reticulum. [3H] cholesteryl ester accumulated in cells prelabeled with [3H] cholesterol, confirming that serum amyloid A mediated the movement of endogenous cholesterol. Cholesterol movement was dependent on functional endolysosomes. The cholesterol oxidase–sensitive pool of cholesterol decreased in serum amyloid A−treated cells. Furthermore, the mechanism whereby serum amyloid A induced cholesterol trafficking was determined to be via activation of expression of secretory phospholipase A2, group IIA (secretory phospholipase A2) and secretory phospholipase A2–dependent activation of sphingomyelinase. Interestingly, although neither tumor necrosis factor-α nor interferon-γ induced cholesterol trafficking, interleukin-1ß induced [14C] cholesteryl ester accumulation that was also dependent upon secretory phospholipase A2 and sphingomyelinase activities. Serum amyloid A activates smooth muscle cell interleukin-1ß expression, and although the interleukin-1—receptor antagonist inhibited the interleukin-1ß−induced cholesterol trafficking, it had no effect on the movement of cholesterol mediated by serum amyloid A.
Conclusion—These data support a role for inflammation in endogenous smooth muscle cell cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.
- Received August 1, 2012.
- Accepted August 8, 2012.
- © 2012 American Heart Association, Inc.