Peng Li1, Jian Wu2, Li Zhao1, Xue-Wei Feng3. 1. Department of Respiratory Medicine, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, China. 2. Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China. 3. Department of Respiratory Medicine, Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, China. iziatnas@163.com.
Abstract
OBJECTIVE: This study investigated the influence of intermittent hypoxia on serum lipid level, hepatic low-density lipoprotein receptor-related protein (LRP)1, and hepatic hypoxia-inducible factor (HIF)-1α and the underlying mechanisms of action. METHODS: Male Sprague Dawley rats were subjected to different levels of hypoxia. After 1-4 weeks hypoxemia, routine blood tests were performed and the levels of LRP1 and HIF-1α in liver were examined. Intermittent hypoxia (IH) was induced in HepG2 cells with or without HIF-1α inhibitor YC-1 pretreatment, and the levels of LRP1 and HIF-1α in cells were examined. RESULTS: IH caused elevated serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein in rats. IH caused elevated hepatic levels of LRP1 and HIF-1α. After pretreatment with YC-1, HIF-1α protein expression decreased but mRNA expression did not change in HepG2 cells. CONCLUSIONS: IH caused dyslipidemia and elevated LRP1 and HIF-1α. Elevated LRP1 expression was caused by HIF-1α.
OBJECTIVE: This study investigated the influence of intermittent hypoxia on serum lipid level, hepatic low-density lipoprotein receptor-related protein (LRP)1, and hepatic hypoxia-inducible factor (HIF)-1α and the underlying mechanisms of action. METHODS: Male Sprague Dawley rats were subjected to different levels of hypoxia. After 1-4 weeks hypoxemia, routine blood tests were performed and the levels of LRP1 and HIF-1α in liver were examined. Intermittent hypoxia (IH) was induced in HepG2 cells with or without HIF-1α inhibitor YC-1 pretreatment, and the levels of LRP1 and HIF-1α in cells were examined. RESULTS: IH caused elevated serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein in rats. IH caused elevated hepatic levels of LRP1 and HIF-1α. After pretreatment with YC-1, HIF-1α protein expression decreased but mRNA expression did not change in HepG2 cells. CONCLUSIONS: IH caused dyslipidemia and elevated LRP1 and HIF-1α. Elevated LRP1 expression was caused by HIF-1α.
Entities:
Keywords:
Dyslipidemia; Hypoxia-inducible factor-1α; Intermittent hypoxia; Low-density lipoprotein receptor- related protein 1; YC-1
Authors: Steven R Coughlin; Lynn Mawdsley; Julie A Mugarza; Peter M A Calverley; John P H Wilding Journal: Eur Heart J Date: 2004-05 Impact factor: 29.983