Ablation of Neutral Cholesterol Ester Hydrolase 1 Accelerates Atherosclerosis

作者：Sekiya Motohiro; Osuga Jun ichi; Nagashima Shuichi; Ohshiro Taichi; Igarashi Masaki; Okazaki Hiroaki; Takahashi Manabu; Tazoe Fumiko; Wada Taeko; Ohta Keisuke; Takanashi Mikio; Kumagai Masayoshi; Nishi Makiko; Takase Satoru; Yahagi Naoya; Yagyu Hiroaki; Ohashi Ken; Nagai Ryozo; Kadowaki Takashi; Furukawa Yusuke; Ishibashi Shun^*

来源：Cell Metabolism, 2009, 10(3): 219-228.

DOI：10.1016/j.cmet.2009.08.004

Cholesterol ester (CE)-laden macrophage foam cells are the hallmark of atherosclerosis, and the hydrolysis of intracellular CE is one of the key steps in foam cell formation. Although hormone-sensitive lipase (LIPE) and cholesterol ester hydrolase (CEH), which is identical to carboxylsterase 1 (CES1, hCE1), were proposed to mediate the neutral CE hydrolase (nCEH) activity in macrophages, recent evidences have suggested the involvement of other enzymes. We have recently reported the identification of a candidate, neutral cholesterol ester hydrolase 1 (Nceh1). Here we demonstrate that genetic ablation of Nceh1 promotes foam cell formation and the development of atherosclerosis in mice. We further demonstrate that Nceh1 and Lipe mediate a comparable degree of nCEH activity in macrophages; and together account for most of the activity. Mice lacking both Nceh1 and Lipe aggravated atherosclerosis in an additive manner. Thus, Nceh1 is a promising target for the treatment of atherosclerosis.

• 出版日期2009-9-2