This article is part of the Topical Collection on Lipid Abnormalities and Cardiovascular Prevention
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.
Varbo A, Benn M, Tybjaerg-Hansen A, et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61:427–36. This excellent paper describes the association between plasma levels of remnant cholesterol and ischemic heart disease in a large population cohort in Denmark and illustrates the importance of remnant cholesterol in the pathokogy of CVD. CrossRefPubMed
Emerging Risk Factors C, Di Angelantonio E, Gao P, et al. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307:2499–506.
Chapman MJ, Ginsberg HN, Amarenco P, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32:1345–61. This is an important paper describing new guidelines with regard to the treatment of patients with elevated levels of remnant cholesterol and triglycerides. CrossRefPubMedPubMedCentral
Triglyceride Coronary Disease Genetics C, Emerging Risk Factors C, Sarwar N, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375:1634–9. CrossRef
Kersten S. Physiological regulation of lipoprotein lipase. Biochim Biophys Acta. 1841;2014:919–33.
Sakurai T, Sakurai A, Vaisman BL et al. Creation of ApoC-II mutant mice and correction of their hypertriglyceridemia with an ApoC-II mimetic peptide. J Pharmacol Exp Ther. 2016;356:341–353.
TG, HDL Working Group of the Exome Sequencing Project NHL, Blood I, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371:22–31.
Shu X, Nelbach L, Weinstein MM, et al. Intravenous injection of apolipoprotein A-V reconstituted high-density lipoprotein decreases hypertriglyceridemia in apoav−/− mice and requires glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1. Arterioscler Thromb Vasc Biol. 2010;30:2504–9. CrossRefPubMedPubMedCentral
Hiukka A, Fruchart-Najib J, Leinonen E, et al. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes. Diabetes. 2005;48:1207–15.
Ginsberg HN, Le NA, Goldberg IJ, et al. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. J Clin Invest. 1986;78:1287–95. CrossRefPubMedPubMedCentral
Cohn JS, Johnson EJ, Millar JS, et al. Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters. J Lipid Res. 1993;34:2033–40. PubMed
- Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?
Geesje M. Dallinga-Thie
M. John Chapman
- Springer US
Neu im Fachgebiet Kardiologie
Mail Icon II