Trafficking of Endogenous Smooth Muscle Cell Cholesterol: A Role for Serum Amyloid A and Interleukin-1β

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 32; no. 11; pp. 2741 - 2750
• Main Authors: Pessolano, Lawrence G, Sullivan, Christopher P, Seidl, Stephanie E, Rich, Celeste B, Liscum, Laura, Stone, Phillip J, Sipe, Jean D, Schreiber, Barbara M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-11-2012; Lippincott Williams & Wilkins
• Subjects: Animals; Animals, Newborn; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biological Transport; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cells, Cultured; Cholesterol - metabolism; Cholesterol Esters - metabolism; Cholesterol Oxidase - metabolism; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endoplasmic Reticulum - metabolism; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Inflammation Mediators - metabolism; Interferon-gamma - metabolism; Interleukin 1 Receptor Antagonist Protein - pharmacology; Interleukin-1beta - metabolism; Lipoproteins, IDL - metabolism; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Oleic Acid - metabolism; Phospholipases A2, Secretory - antagonists & inhibitors; Phospholipases A2, Secretory - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Interleukin-1 - metabolism; Serum Amyloid A Protein - metabolism; Sphingomyelin Phosphodiesterase - antagonists & inhibitors; Sphingomyelin Phosphodiesterase - metabolism; Time Factors; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: cardiovascular system; serum amyloid A; Cytokine; cholesterol trafficking; Lipids; Interleukin 1β; Smooth muscle; Cardiovascular disease; Cholesterol; interleukin-1β; Vascular disease; smooth muscle cells; Atherosclerosis; Amyloid
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.112.300243

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 increased [C] oleic acid incorporation into cholesteryl ester in rat smooth muscle cells, suggesting endogenous cholesterol trafficking to the endoplasmic reticulum. [H] cholesteryl ester accumulated in cells prelabeled with [H] cholesterol, confirming that serum amyloid A mediated the movement of endogenous cholesterol. Cholesterol movement was dependent upon 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 (sPLA2) and sPLA2–dependent activation of sphingomyelinase. Interestingly, although neither tumor necrosis factor-α nor interferon-γ induced cholesterol trafficking, interleukin-1β induced [C] cholesteryl ester accumulation that was also dependent upon sPLA2 and sphingomyelinase activities. Serum amyloid A activates smooth muscle cell interleukin-1β expression, and although the interleukin-1–receptor antagonist inhibited the interleukin-1β−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.