What Is Apolipoprotein C?
Apolipoproteins are proteins that tend to bind with the lipids to form lipoproteins and their main function is to boost the transportation of lipids. Apolipoproteins are significant in retaining the structural integrity and solubility of lipoproteins and play a crucial part in lipoprotein receptor distinction and the regulation of particular enzymes in lipoprotein metabolism. There are six main types of apolipoprotein: A, B, C, D, E, and H.
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Apolipoprotein C: The apolipoprotein C family primarily comprises three closely connected proteins—apo C-I, apo C-II, and apo C-III. These are mainly produced by the liver and to some extent, in the intestine.
What Are the Functions of Apolipoprotein C?
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Apolipoprotein C triggers lipoprotein lipase in capillaries.
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It receives fatty acids and monoglycerides from chylomicrons. These fatty acids then move into adipocytes or muscles.
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The main role of apolipoprotein C-II is to improve triglyceride hydrolysis of very low-density lipoproteins for energy depository.
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These lipoproteins also help in the activation of transcription factors and nuclear hormone receptors
What Are the Disorders Related to Apolipoprotein C?
Apolipoprotein C-III and Cardiovascular Pathophysiology:Several studies have shown that there is a strong correlation between apolipoprotein C with a high-risk of devcardiovascular diseases such as coronary artery disease. It is evident that the variation in the levels of plasma apolipoprotein C leads to atherogenicity, that is, the formation of abnormal fatty or lipid masses in arterial walls. Therefore, these lipoproteins play an important role in counting cardiovascular risk. Primarily these apolipoproteins C impede the discharge of triglyceride-rich lipoprotein remnants, enriching their plasma levels and extending their dwelling period in the blood. Hence it has been proved that apolipoprotein C is the key factor for cardiovascular disease onset and progression exhibiting atherogenic properties.
ApoC-III Links Dyslipidemia With CVD:All the dispersed lipoproteins usually flux into and out of the arterial wall by the process of transcytosis, that is, a transport system by which these lipoproteins get transported with the help of specialized vesicles present across the endothelial membrane. These transport vesicles are clathrin-coated, about one hundred nanometers in diameter which makes the transcytotic system impermeable to lipoproteins smaller than the size of seventy nanometers. But these remnants are small enough to infiltrate the arterial intima. The triglyceride-rich lipoproteins are enriched with cholesterol, around 40 times more than low-density level lipoprotein. Hence, they instantly intercede cholesterol deposition within the arterial intima and stimulate the activation of different inflammatory approaches. As in the case of cardiovascular diseases, there is an increased level of apolipoprotein C-III which indicates that there is enhanced atherosclerosis. The plasma components present in the arterial walls along with plaque accumulation stimulate the process of atherosclerosis.
ApoC-III Is Directly Involved in Atherosclerosis:Various studies have already proved the fact that apolipoprotein C has the tendency of atherogenicity, rather than increasing the levels of triglycerides in the blood vessels. The prominent sites of atherosclerotic lesions are the coronary artery, the carotid artery, and the aorta. Patients with high levels of apolipoprotein C carry a raised risk of both fatal and nonfatal myocardial infarction. Apolipoprotein C-III facilitates the phosphatidylcholine-specific phospholipase C (PC) action, and this further catalyzes the phospholipase C to develop phosphatidylcholine and diacylglycerol (DAG). The diacylglycerol then activates the protein kinase C alpha (an enzyme involved in proliferation of the cell and cell growth arrest by positive and negative regulation of the cell cycle). This leads to the translocation of NFκB (nuclear factor kappa beta) into the nuclei, where it boosts the transcription of the gene encoding the β1-integrin (involved in cell adhesion and embryogenesis, tissue repair, hemostasis, immune response, and metastatic diffusion of tumor cells). The following are the factors responsible for the establishment of atherosclerosis:
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Apolipoprotein triggers the proliferation of smooth muscle cells. Cells enriched with triglyceride-rich lipoproteins are responsible for smooth muscle cell proliferation and arterial stenosis.
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Arterial wall inflammation caused by an accumulation of lipoproteins.
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There is an increase in the levels of apolipoprotein C due to endothelial dysfunction, placement of blood monocytes to the zone of injury, and their successive extravasation through the endothelium into the sub-endothelial area.
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There is an increased adhesiveness of endothelial cells to the apolipoproteins.
ApoC-III Alters HDL Functionality:High-density lipoprotein (HDL) or the ‘good’ cholesterol helpsto remove different forms of cholesterol from the bloodstream. The variations in the levels of apolipoprotein C is known to cause the alteration in the functions and structure of high-density lipoproteins. The high-density lipoprotein possesses many anti-inflammatory and anti-apoptotic properties. High-density lipoprotein also retains the property of reverse efflux mechanism by which helps the body to remove excess cholesterol from peripheral tissues and delivers them to the liver, where it will be redistributed to other tissues or withdrawn from the body by the gallbladder. But all these characteristics of high-density lipoproteins get altered in many pathological conditions such as cardiovascular diseases. All the above-mentioned properties of high-density lipoprotein show a strong correlation with the dysfunctionality in their levels that occur due to abnormalities in the levels of apolipoprotein C. Various proteomics investigations have been done in which high-density lipoprotein particles are sequestered from patients suffering from cardiovascular diseases. It is seen that these isolated high-density lipoproteins show enriched atherogenic properties. Studies have also proved that apolipoprotein C-III is accountable for the activation of the p38-mitogen-activated protein kinase signaling pathway in endothelial cell development, pursued by a disproportionate manifestation of the pro-apoptotic protein truncated-BID (BH3 interacting-domain death agonist), thus, transforming high-density lipoprotein from cytoprotective into pro-apoptotic molecules.
Conclusion
Apolipoprotein C plays an important role in triglyceride homeostasis, inflammation, and atherosclerosis. Recent studies have also shown that the variation in the levels of apolipoprotein C augments the risk in patients suffering from cardiovascular diseases such as coronary artery disease. The article reviews the disorders related to apolipoprotein C like atherosclerosis, dyslipidemia, and the levels of high-density lipoproteins.
