Apolipoprotein C-III also known as apo-CIII, and apolipoprotein C3, is a protein that in humans is encoded by the APOC3 gene.
Apo-CIII is secreted by the liver as well as the small intestine, and is found on triglyceride-rich lipoproteins such as chylomicrons, very low density lipoprotein (VLDL), and remnant cholesterol.
Chromosome 11
ApoC-III is a relatively small protein containing 79 amino acids,
APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake of triglyceride-rich particles.
The APOA1, APOC3 and APOA4 genes are closely linked in both rat and human genomes.
An increase in apoC-III levels induces the development of hypertriglyceridemia.
APOC3 resides in the surface of all lipoproteins, chylomicrons, and VLDL, LDL, protein a, and HDL particles and affects plasma triglyceride levels by inhibiting lipoprotein lipase mediated triglyceride rich lipoprotein metabolism, and its uptake by hepatocytes leading to increase levels of circulating chylomicrons and triglyceride rich lipoproteins.
APOC3 loss of function variance or associated with reduced plasma, triglyceride levels protection against coronary heart disease, and increased longevity.
APOC3 is associated with reduction in triglyceride and remnant cholesterol levels and the risk of atherosclerotic cardiovascular disease of approximately 40%.
5% of Amish have an APO C3 loss of function variant, yielding lower triglyceride rich lipoproteins, increased HDL cholesterol and reduce burden of coronary atherosclerosis.
Some European populations with APOC3 loss of function variants have similar lipid panels and a low incidence of coronary artery disease.
Overexpression of Apo-C3 in humans contributes to atherosclerosis.
In people with type 2 diabetes, elevated plasma Apo-C3is associated with higher plasma triglycerides and greater coronary artery calcification, a measure of subclinical atherosclerosis.
Apo-CIII delays the catabolism of triglyceride rich particles.
HDL cholesterol particles that bear Apo-CIII are associated with increased, rather than decreased, risk for coronary heart disease.
Elevations of Apo-CIII associated with single-nucleotide polymorphisms found in genetic variation studies may predispose patients to non-alcoholic fatty liver disease: and may be specific to certain ethnicities or to people without central obesity.
Antisense oligonucleotides that bind APOC3 mRNA and prevent its translation have been found to reduce episodes of acute pancreatitis in people with familial chylomicronemia syndrome and lower their triglyceride levels in blood.
Apolipoprotein CIII is also found on HDL particles.
Accumulation of APOCIII on HDL is important for the maintenance of plasma triglyceride homeostasis since it prevents excessive amount of APOCIII on VLDL and other triglyceride rich lipoproteins, thus preventing APOCIII-mediated inhibition of LpL and the subsequent hydrolysis of plasma triglycerides.
Pharmacologic approaches to reduce APO C3 expression include Gene silencing with antisense oligonucleotides or small interfering RNA .
In a randomized control trial with participants with mixed hyper lipidemia Plozasiran an RNA interference agent targeting APOC3 significantly reduced triglyceride levels at 24 weeks.