Ablation of Neutral Cholesterol Ester Hydrolase 1 Accelerates Atherosclerosis

详细信息    查看全文

• 作者：Motohiro Sekiya ; Jun-ichi Osuga ; Shuichi Nagashima ; Taichi Ohshiro ; Masaki Igarashi ; Hiroaki Okazaki ; Manabu Takahashi ; Fumiko Tazoe ; Taeko Wada ; Keisuke Ohta ; Mikio Takanashi ; Masayoshi Kumagai ; Makiko Nishi ; Satoru Takase ; Naoya Yahagi ; Hiroaki Yagyu ; Ken Ohashi ; Ryozo Nagai ; Takashi Kadowaki ; Yus
• 刊名：Cell Metabolism
• 出版年：2009
• 出版时间：2 September 2009
• 年：2009
• 卷：10
• 期：3
• 页码：219-228
• 全文大小：1523 K

文摘

Summary

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.