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Roles of 7-ketocholesterol on the Homeostasis of Intracellular Cholesterol Level

Son, Yonghae PhD; Kim, Koanhoi PhD; Kim, Sunmi PhD; Lee, Sae-A MS; Jang, Hyojung MS; Rhim, Byung-Yong MD, PhD

Journal of Cardiovascular Pharmacology: August 2012 - Volume 60 - Issue 2 - p 199–207
doi: 10.1097/FJC.0b013e31825c3ddc
Original Article

Abstract: Atherosclerotic plaque contains materials, such as cholesterol, oxysterols, cell debris, modified fatty acids, and infiltrated cells. Among them, cholesterol is the major component in plaque. Cholesterol is known to originate from the influx of extracellular materials, but this explanation is not enough for the cholesterol accumulation observed in atherosclerotic plaque. This study examined the origins of cholesterols in plaques. The main focus was to determine if the intracellular cholesterol levels are affected by oxysterols in human vascular smooth muscle cells. The results showed that the cholesterol levels increased in response to a 7-ketocholesterol (7K)-treatment in a dose-dependent manner. Eight enzymes involved in cholesterol biosynthesis were examined. Among them, squalene epoxidase (SQLE) was increased by 7K but not by 7α-hydroxycholesterol, 27-hydroxycholesterol (27OH-chol), or cholesterol. The 7K-induced SQLE expression was suppressed in the presence of the enzyme inhibitor SB203580 but not by UO126 and SP600125. The SQLE immunoreactivity was detected in the atherosclerotic plaque of the aortic roots from apoE−/− mice. In addition, 7K increased the cholesterol level and SQLE expression in murine bone marrow–derived macrophages. This suggests that 7K increases the intracellular cholesterol level through an elevation of SQLE expression, which might affect the progress of cholesterol accumulation in the atherosclerotic lipid core.

Department of Pharmacology, School of Medicine, Pusan National University, Busan, Korea.

Reprints: Byung-Yong Rhim, MD, PhD, Department of Pharmacology, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan, Gyoengnam 626-870, Republic of Korea (e-mail: byrhim@pusan.ac.kr).

Supported financially by the 2011 Post-Doc. Development Program of Pusan National University.

The authors report no conflicts of interest.

Received January 4, 2012

Accepted April 25, 2012

© 2012 Lippincott Williams & Wilkins, Inc.