ANGPTL3 and Apolipoprotein C-III as Novel Lipid-Lowering Targets

2021 ◽  
Vol 23 (5) ◽  
Author(s):  
Ioannis Akoumianakis ◽  
Evangelia Zvintzou ◽  
Kyriakos Kypreos ◽  
Theodosios D. Filippatos
2005 ◽  
Vol 51 (2) ◽  
pp. 360-367 ◽  
Author(s):  
Oliviero Olivieri ◽  
Nicola Martinelli ◽  
Marco Sandri ◽  
Antonella Bassi ◽  
Patrizia Guarini ◽  
...  

Abstract Background: Apolipoprotein C-III (apo C-III) is a marker of cardiovascular disease risk associated with triglyceride (TG)-rich lipoproteins. The T−455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apo C-III concentrations. Long-chain n-3 polyunsaturated fatty acids (PUFAs) contained in fish have well-known apo C-III-lowering properties. Methods: We investigated the possibility of an interactive effect between the APOC3 gene variant and erythrocyte n-3 PUFAs, suitable markers of dietary intake of fatty acids, on apo C-III concentrations in a population of 848 heart disease patients who had coronary angiography. Results: In the population as a whole, apo C-III concentrations were significantly inversely correlated with total erythrocyte PUFAs, but the correlation was not significant when only −455CC homozygous individuals were taken into account. In the total population and in subgroups with the −455TT and −455CT genotypes, the relative proportions of individuals presenting with increased apo C-III (i.e., above the 75th percentile value calculated on the entire population after exclusion of individuals taking lipids-lowering medications) decreased progressively as the n-3 PUFA and docosahexaenoic acid concentrations increased. The opposite situation was observed in the homozygous −455CC subgroup, in whom increasing erythrocyte n-3 PUFA and docosahexaenoic acid concentrations were associated with higher proportions of individuals with high apo C-III. A formal interactive effect between genotype and n-3 PUFAs was confirmed even after adjustment for possible confounding variables [age, sex, body mass index, smoking, coronary artery disease (CAD)/CAD-free status, or use of lipid-lowering medications] by logistic models. Conclusion: Patients homozygous for the −455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs.


2019 ◽  
Vol 8 (7) ◽  
pp. 1085 ◽  
Author(s):  
Zwol ◽  
Rimbert ◽  
Kuivenhoven

The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD. This review summarizes the evidence and the rationale to target Lp(a) and triglycerides and provides an overview of currently tested strategies to lower Lp(a), apolipoprotein C-III and angiopoietin-like protein 3. In addition, it summarizes new findings on the use of omega-3 fatty acids (OM3FA) to fight ASCVD. With the exception of OM3FA supplementation, the promise of the experimental drugs discussed here depends on the long-term safety and efficacy of monoclonal antibodies and/or antisense oligonucleotides Clinical outcome trials will ultimately prove whether these new therapeutic modalities will reduce ASCVD risk.


2011 ◽  
Vol 44 (8) ◽  
pp. 12
Author(s):  
CAROLINE HELWICK
Keyword(s):  

VASA ◽  
2014 ◽  
Vol 43 (3) ◽  
pp. 189-197 ◽  
Author(s):  
Yiqiang Zhan ◽  
Jinming Yu ◽  
Rongjing Ding ◽  
Yihong Sun ◽  
Dayi Hu

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.


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