Abstract:
AIMS: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). METHODS AND RESULTS: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. CONCLUSIONS:CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Drager LF,Li J,Shin MK,Reinke C,Aggarwal NR,Jun JC,Bevans-Fonti S,Sztalryd C,O'Byrne SM,Kroupa O,Olivecrona G,Blaner WS,Polotsky VYdoi
10.1093/eurheartj/ehr097subject
Has Abstractpub_date
2012-03-01 00:00:00pages
783-90issue
6eissn
0195-668Xissn
1522-9645pii
ehr097journal_volume
33pub_type
杂志文章abstract:AIMS:Cardiac biomarkers are routinely elevated after uncomplicated cardiac surgery to levels considered diagnostic of myocardial infarction in ambulatory populations. We investigated the diagnostic power of electrocardiogram (ECG) and cardiac biomarker criteria to predict clinically relevant myocardial injury using ben...
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更新日期:2020-12-16 00:00:00