Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
Eur Heart J. 2012 Mar;33(6):783-90. doi: 10.1093/eurheartj/ehr097. Epub 2011 Apr 9.
Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP).
Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO(2) was decreased to 6.5% once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P< 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P< 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a >5-fold decrease in LpL activity (P< 0.01) and an 80% increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart.
CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.
脂蛋白清除延迟与动脉粥样硬化有关。本研究探讨了阻塞性睡眠呼吸暂停（OSA）的标志性特征——慢性间歇性低氧（CIH）是否通过抑制富含甘油三酯的脂蛋白（TRLP）的清除而导致高脂血症。
雄性 C57BL/6J 高脂饮食小鼠接受 4 周的 CIH 或慢性间歇性空气（对照）暴露。CIH 组在 12 小时光照期间，每 1 分钟将 FIO2 降低到 6.5%。暴露后，我们测量了空腹血脂谱。通过口服棕榈酸视黄酯后测量血清视黄酯（RE），在 0、1、2、4、10 和 24 小时评估 TRLP 清除率。测定了脂肪组织、骨骼肌和心脏中脂蛋白脂酶（LpL）的活性，LpL 是脂蛋白清除的关键酶，以及血管生成素样蛋白 4（Angptl4）的水平，Angptl4 是 LpL 活性的一种强有力的抑制剂。慢性间歇性低氧导致总胆固醇和甘油三酯水平显著升高，这发生在 TRLP 和 LDL 部分（每种比较均 P<0.05）。与对照组相比，暴露于 CIH 的动物在口服棕榈酸视黄酯后 10 小时内 REs 增加（P<0.05），表明 CIH 抑制了 TRLP 清除。CIH 导致脂肪组织中 LpL 活性降低了>5 倍（P<0.01），Angptl4 mRNA 和蛋白水平增加了 80%，但在骨骼肌或心脏中没有增加。
CIH 降低 TRLP 清除率并抑制脂肪组织中的 LpL 活性，这可能导致 OSA 中观察到的动脉粥样硬化形成。
