title: Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?
abstract: It is now evident that elevated circulating levels of triglycerides in the non-fasting state, a marker for triglyceride (TG)-rich remnant particles, are associated with increased risk of premature cardiovascular disease (CVD). Recent findings from basic and clinical studies have begun to elucidate the mechanisms that contribute to the atherogenicity of these apoB-containing particles. Here, we review current knowledge of the formation, intravascular remodelling and catabolism of TG-rich lipoproteins and highlight (i) the pivotal players involved in this process, including lipoprotein lipase, glycosylphosphatidylinositol HDL binding protein 1 (GPIHBP1), apolipoprotein (apo) C-II, apoC-III, angiopoietin-like protein (ANGPTL) 3, 4 and 8, apoA-V and cholesteryl ester transfer protein; (ii) key determinants of triglyceride (TG) levels and notably rates of production of very-low-density lipoprotein 1 (VLDL1) particles; and (iii) the mechanisms which underlie the atherogenicity of remnant particles. Finally, we emphasise the polygenic nature of moderate hypertriglyceridemia and briefly discuss modalities for its clinical management. Several new therapeutic strategies to attenuate hypertriglyceridemia have appeared recently, among which those targeted to apoC-III appear to hold considerable promise.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. g.m.dallinga@amc.uva.nl.|Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. g.m.dallinga@amc.uva.nl.
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.|Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kroon
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.affiliation: INSERM and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, 75651, Paris Cedex 13, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
mesh_terms: D050197:Atherosclerosis / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood*; D058990:Molecular Targeted Therapy / Q000379:methods*; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood*
chemical_list: D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride; C112017:remnant-like particle cholesterol; D002784:Cholesterol
keywords: Apolipoprotein; Heparin sulphate proteoglycan; Triglycerides