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APOC3: Triglycerides do matter.

Hassan M - Glob Cardiol Sci Pract (2014)

View Article: PubMed Central - PubMed

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High plasma triglyceride (TG) levels are commonly encountered in clinical practice; 30% of the adult US population has a TG level above 150 mg/dL... Hypertriglyceridemia is perceived to be associated with increased risk of coronary heart disease (CHD) in many epidemiological studies, however the independency of TG level as a causal risk factor in promoting cardiovascular (CV) disease has remained a matter of debate for more than 3 decades... APOC3 inhibits TRL hydrolysis and promotes pro-atherogenic responses in macrophages and endothelial cells through activation of adhesion and pro-inflammatory molecules expression, and impairment of endothelial nitric oxide production and insulin signaling pathways... Carriers of a mutation (R19X) in APOC3 gene in the genome-wide association study (GWAS) had significantly lower triglyceride levels, higher HDL-C level, and reduced coronary artery calcification compared to non-carriers, suggesting a potential cardioprotective effect for lifelong deficiency of APOC3... Data from the TG and HDL Working Group of the Exome Sequencing Project provide insights into the association between APOC3 genotype, plasma lipid profile, and risk of clinical CHD... Carriers of any of these mutations had 39% lower plasma TG levels (84.5 vs. 137.5 mg/dL respectively, p = 6 × 10), 22% higher HDL-C levels (61.9 vs. 50.7 mg/dL respectively, p = 3 × 10), and 16% lower LDL-C levels (122.8 vs. 146.2 mg/dL respectively, p = 0.05) than non-carriers... Growing evidence from genetic studies has renewed interest in the potential association between elevated triglycerides concentrations and increased risk of CV diseases, specifically after the grave doubts about the power of HDL-C as a causal CV risk factor... Recently published data from Copenhagen City Heart Study (CCHS) and Copenhagen General Population Study (CGPS) have confirmed a significantly lower incidence of CHD in participants with non-fasting triglyceride levels of less than 1.00 mmol/L (90 mg/dL), compared to those with levels of 4.00 mmol/L(350 mg/dL) or more (hazard ratio = 0.40; 95% CI = 0.31 to 0.52, p < 0.01)... In addition, the use of statins, thiazolidinediones, ezetimibe, niacin, fish oil and weight loss, has been associated with decreases in plasma APOC3 levels... In the same context, Kathiresan et al. has recently confirmed a highly significant association between the effects of single nucleotide polymorphism (SNPs) on triglyceride levels and CHD risk, even after accounting for their confounding effect on HDL-C or LDL-C levels... Regulating APOC3 metabolism may be an important novel therapeutic approach in the near future to manage dyslipidemia and reduce CVD risk - in a manner similar to the development of monoclonal antibodies directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) based on the original data derived from PCSK9 gene studies... In fact, an antisense oligonucleotide therapeutic agent that decreases the production of APOC3 has recently been investigated and shown to be associated with reduced plasma TG levels in mice, nonhuman primates, and healthy human volunteers... Low HDL-C might merely be a marker of raised triglycerides and remnant cholesterol... These data may renew the potential benefit of therapeutic lowering of triglyceride levels to reduce the risk of CAD.

No MeSH data available.


3D structure of human apolipoprotein C3 (APOC3). Image shows the NMR structures of the front (left) and back (right). This representation shows the secondary structures [helices are cyan and turns, pink].
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fig1: 3D structure of human apolipoprotein C3 (APOC3). Image shows the NMR structures of the front (left) and back (right). This representation shows the secondary structures [helices are cyan and turns, pink].

Mentions: APOC3 – a 79-amino acid glycoprotein that is a major component of circulating TRL – (Figure 1) has received recently increasing attention. APOC3 inhibits TRL hydrolysis and promotes pro-atherogenic responses in macrophages and endothelial cells through activation of adhesion and pro-inflammatory molecules expression, and impairment of endothelial nitric oxide production and insulin signaling pathways.7,8 Carriers of a mutation (R19X) in APOC3 gene in the genome-wide association study (GWAS) had significantly lower triglyceride levels, higher HDL-C level, and reduced coronary artery calcification compared to non-carriers, suggesting a potential cardioprotective effect for lifelong deficiency of APOC3.8


APOC3: Triglycerides do matter.

Hassan M - Glob Cardiol Sci Pract (2014)

3D structure of human apolipoprotein C3 (APOC3). Image shows the NMR structures of the front (left) and back (right). This representation shows the secondary structures [helices are cyan and turns, pink].
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4352677&req=5

fig1: 3D structure of human apolipoprotein C3 (APOC3). Image shows the NMR structures of the front (left) and back (right). This representation shows the secondary structures [helices are cyan and turns, pink].
Mentions: APOC3 – a 79-amino acid glycoprotein that is a major component of circulating TRL – (Figure 1) has received recently increasing attention. APOC3 inhibits TRL hydrolysis and promotes pro-atherogenic responses in macrophages and endothelial cells through activation of adhesion and pro-inflammatory molecules expression, and impairment of endothelial nitric oxide production and insulin signaling pathways.7,8 Carriers of a mutation (R19X) in APOC3 gene in the genome-wide association study (GWAS) had significantly lower triglyceride levels, higher HDL-C level, and reduced coronary artery calcification compared to non-carriers, suggesting a potential cardioprotective effect for lifelong deficiency of APOC3.8

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

High plasma triglyceride (TG) levels are commonly encountered in clinical practice; 30% of the adult US population has a TG level above 150 mg/dL... Hypertriglyceridemia is perceived to be associated with increased risk of coronary heart disease (CHD) in many epidemiological studies, however the independency of TG level as a causal risk factor in promoting cardiovascular (CV) disease has remained a matter of debate for more than 3 decades... APOC3 inhibits TRL hydrolysis and promotes pro-atherogenic responses in macrophages and endothelial cells through activation of adhesion and pro-inflammatory molecules expression, and impairment of endothelial nitric oxide production and insulin signaling pathways... Carriers of a mutation (R19X) in APOC3 gene in the genome-wide association study (GWAS) had significantly lower triglyceride levels, higher HDL-C level, and reduced coronary artery calcification compared to non-carriers, suggesting a potential cardioprotective effect for lifelong deficiency of APOC3... Data from the TG and HDL Working Group of the Exome Sequencing Project provide insights into the association between APOC3 genotype, plasma lipid profile, and risk of clinical CHD... Carriers of any of these mutations had 39% lower plasma TG levels (84.5 vs. 137.5 mg/dL respectively, p = 6 × 10), 22% higher HDL-C levels (61.9 vs. 50.7 mg/dL respectively, p = 3 × 10), and 16% lower LDL-C levels (122.8 vs. 146.2 mg/dL respectively, p = 0.05) than non-carriers... Growing evidence from genetic studies has renewed interest in the potential association between elevated triglycerides concentrations and increased risk of CV diseases, specifically after the grave doubts about the power of HDL-C as a causal CV risk factor... Recently published data from Copenhagen City Heart Study (CCHS) and Copenhagen General Population Study (CGPS) have confirmed a significantly lower incidence of CHD in participants with non-fasting triglyceride levels of less than 1.00 mmol/L (90 mg/dL), compared to those with levels of 4.00 mmol/L(350 mg/dL) or more (hazard ratio = 0.40; 95% CI = 0.31 to 0.52, p < 0.01)... In addition, the use of statins, thiazolidinediones, ezetimibe, niacin, fish oil and weight loss, has been associated with decreases in plasma APOC3 levels... In the same context, Kathiresan et al. has recently confirmed a highly significant association between the effects of single nucleotide polymorphism (SNPs) on triglyceride levels and CHD risk, even after accounting for their confounding effect on HDL-C or LDL-C levels... Regulating APOC3 metabolism may be an important novel therapeutic approach in the near future to manage dyslipidemia and reduce CVD risk - in a manner similar to the development of monoclonal antibodies directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) based on the original data derived from PCSK9 gene studies... In fact, an antisense oligonucleotide therapeutic agent that decreases the production of APOC3 has recently been investigated and shown to be associated with reduced plasma TG levels in mice, nonhuman primates, and healthy human volunteers... Low HDL-C might merely be a marker of raised triglycerides and remnant cholesterol... These data may renew the potential benefit of therapeutic lowering of triglyceride levels to reduce the risk of CAD.

No MeSH data available.