Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD

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http://hdl.handle.net/10138/302819

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Taskinen , M-R , Packard , C J & Boren , J 2019 , ' Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD ' , Current atherosclerosis reports. , vol. 21 , no. 8 , 27 . https://doi.org/10.1007/s11883-019-0791-9

Title: Emerging Evidence that ApoC-III Inhibitors Provide Novel Options to Reduce the Residual CVD
Author: Taskinen, Marja-Riitta; Packard, Chris J.; Boren, Jan
Contributor: University of Helsinki, Clinicum
Date: 2019-08
Language: eng
Number of pages: 10
Belongs to series: Current atherosclerosis reports.
ISSN: 1523-3804
URI: http://hdl.handle.net/10138/302819
Abstract: Purpose of ReviewApolipoprotein C-III (apoC-III) is known to inhibit lipoprotein lipase (LPL) and function as an important regulator of triglyceride metabolism. In addition, apoC-III has also more recently been identified as an important risk factor for cardiovascular disease. This review summarizes the mechanisms by which apoC-III induces hypertriglyceridemia and promotes atherogenesis, as well as the findings from recent clinical trials using novel strategies for lowering apoC-III.Recent FindingsGenetic studies have identified subjects with heterozygote loss-of-function (LOF) mutations in APOC3, the gene coding for apoC-III. Clinical characterization of these individuals shows that the LOF variants associate with a low-risk lipoprotein profile, in particular reduced plasma triglycerides. Recent results also show that complete deficiency of apoC-III is not a lethal mutation and is associated with very rapid lipolysis of plasma triglyceride-rich lipoproteins (TRL). Ongoing trials based on emerging gene-silencing technologies show that intervention markedly lowers apoC-III levels and, consequently, plasma triglyceride. Unexpectedly, the evidence points to apoC-III not only inhibiting LPL activity but also suppressing removal of TRLs by LPL-independent pathways.SummaryAvailable data clearly show that apoC-III is an important cardiovascular risk factor and that lifelong deficiency of apoC-III is cardioprotective. Novel therapies have been developed, and results from recent clinical trials indicate that effective reduction of plasma triglycerides by inhibition of apoC-III might be a promising strategy in management of severe hypertriglyceridemia and, more generally, a novel approach to CHD prevention in those with elevated plasma triglyceride.
Subject: ApoC-III
Lipoproteins
Triglycerides
Remnants
CVD
genetic variants
APOLIPOPROTEIN-C-III
OF-FUNCTION MUTATIONS
LOW-DENSITY LIPOPROTEINS
LIPID-BINDING
ATHEROGENIC LIPOPROTEINS
HYPOLIPIDEMIC ACTION
ENDOTHELIAL-CELLS
LDL SUBCLASSES
PLASMA-LIPIDS
CIII
3121 General medicine, internal medicine and other clinical medicine
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