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Korean Circ J. 2018 Dec;48(12):1097-1119. doi: 10.4070/kcj.2018.0343.

Triglyceride-Rich Lipoproteins and Novel Targets for Anti-atherosclerotic Therapy.

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1
Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Zagreb, Croatia. zreiner@kbc-zagreb.hr.

Abstract

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

KEYWORDS:

Cardiovascular diseases; Fibrates; Omega-3 fatty acids; Triglycerides; Volanesorsen

PMID:
30403015
PMCID:
PMC6221868
[Available on 2018-12-01]
DOI:
10.4070/kcj.2018.0343
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Conflict of interest statement

The author has received honoraria from Sanofi Aventis and Akcea.

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