Abstract
ContextNonfasting (postprandial) triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs) in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglycan (HSPG) pathway is important for the hepatic clearance of remnant TRLs in mice, but its relevance in humans is unclear. ObjectiveWe sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. Patients And DesignWe performed an oral fat load in 68 healthy subjects. Lipoproteins (chylomicrons and very low density lipoproteins 1 and 2) were isolated from blood, and the area under curve and incremental area under curve for postprandial variables were calculated. Single nucleotide polymorphisms in genes encoding syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were genotyped in the study subjects.ResultsOur results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279 in SULF2 associates with hepatic SULF2 mRNA levels.ConclusionsIn humans, mild but clinically relevant postprandial hyperlipidemia due to reduced hepatic clearance of remnant TRLs may result from genetic polymorphisms that affect hepatic HSPG.
Highlights
Nonfasting triglyceride (TG) concentrations are a clinically significant risk factor for cardiovascular disease (CVD) [1,2,3]
Lipoproteins were isolated and associations between responses of the postprandial lipids and common Single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the synthesis or degradation of heparan sulfate proteoglycan (HSPG) were analyzed
We set up this study to test whether polymorphisms in genes responsible for HSPG assembly or disassembly associate with atherogenic dyslipoproteinemias in humans
Summary
Nonfasting (postprandial) triglyceride (TG) concentrations are a clinically significant risk factor for cardiovascular disease (CVD) [1,2,3]. TGs are carried in chylomicrons (CMs) synthesized in the intestine and in liver-derived very low density lipoprotein (VLDL). Lipolysis of these triglyceride-rich lipoproteins (TRLs) by lipoprotein lipase (LPL) results in the formation of smaller remnants particles that are depleted of triglycerides and enriched in cholesteryl esters [4]. A key step in atherogenesis is entrapment of lipoproteins in the arterial intima [9,10,11]. Because of their size, most remnant particles cannot cross the endothelium as efficiently as smaller low density lipoprotein (LDL) particles [12]. Since each remnant particle contain more cholesteryl esters per particle than do LDL [12], elevated levels of remnants may lead to accelerated atherosclerosis and CVD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
