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Lipoproteins are complex particles that transport lipids, such as phospholipids, triglycerides, and cholesterol, between cells. There are 5 different types of lipoproteins, which are classified according to their density and composition: chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). As per its denomination, HDL has the highest density of lipoproteins and the highest proportion of proteins to lipids.[1] HDL is particularly interesting in medicine, as research has shown a strong inverse association between HDL cholesterol concentration and the risk of atherosclerosis (see Image. Lipoprotein Metabolism).[2]

The ability of HDL to uptake and return excess cholesterol from peripheral tissues back to the liver is of particular interest because of its role in preventing atherosclerosis, the precursor to myocardial infarction, transient ischemic attack, and stroke. Atherosclerosis generally begins in areas of nonlaminar flow, such as branch points and the inner curvature of arteries. This nonlaminar flow increases the shear stress of the artery wall and results in inflammation and activation of the NF-κB pathway. The NF-κB pathway leads to the expression of adhesin molecules, which recruits macrophages to the intima of the artery wall. Simultaneously, the turbulent flow of the blood in the arteries also leads to the disruption of the tight junctions between the endothelium of the artery, resulting in the deposition of LDL and macrophages. In the intima of the artery, the LDL particles undergo oxidation, leading to the macrophages' prolonged activation in the intima and further cascades of inflammation. These macrophages bind and uptake the oxidized LDL, process the LDL cholesterol, and store the cholesterol as cytoplasmic droplets. These cholesterol-filled macrophages have a foamy appearance and are called foam cells. Unfortunately, these foam cells remain in the intima of the artery and continue to promote inflammation, increasing the size of the atherosclerotic plaque. Eventually, these atherosclerotic plaques close the vessel's lumen, leading to angina symptoms. When the plaques eventually rupture, they lead to thrombosis and subsequent occlusion of the artery lumen, resulting in the previously mentioned cardiovascular events.[10][11][12]

The ability of HDL to uptake and return excess cholesterol from peripheral tissues back to the liver is of particular interest because of its role in preventing atherosclerosis, the precursor to myocardial infarction, transient ischemic attack, and stroke. Atherosclerosis generally begins in areas of nonlaminar flow, such as branch points and the inner curvature of arteries. This nonlaminar flow increases the shear stress of the artery wall and results in inflammation and activation of the NF-κB pathway. The NF-κB pathway leads to the expression of adhesin molecules, which recruits macrophages to the intima of the artery wall. Simultaneously, the turbulent flow of the blood in the arteries also leads to the disruption of the tight junctions between the endothelium of the artery, resulting in the deposition of LDL and macrophages. In the intima of the artery, the LDL particles undergo oxidation, leading to the macrophages' prolonged activation in the intima and further cascades of inflammation. These macrophages bind and uptake the oxidized LDL, process the LDL cholesterol, and store the cholesterol as cytoplasmic droplets. These cholesterol-filled macrophages have a foamy appearance and are called foam cells. Unfortunately, these foam cells remain in the intima of the artery and continue to promote inflammation, increasing the size of the atherosclerotic plaque. Eventually, these atherosclerotic plaques close the vessel's lumen, leading to angina symptoms. When the plaques eventually rupture, they lead to thrombosis and subsequent occlusion of the artery lumen, resulting in the previously mentioned cardiovascular events.[10][11][12] HDL is of interest in atherosclerosis as it can extract cholesterol from foam cells and lead to the remission of atherosclerotic plaque. Specifically, the free cholesterol synthesized in the foam cells is effluxed by ABCA1, SR-B1, and ABCG1 into already circulating HDL or onto Apo-AI or Apo-E discs, forming HDL. In this manner, HDL is considered an antiinflammatory, as it removes free cholesterol from foam cells and results in the down-regulation of inflammation within the atherosclerotic plaque. However, it bears mentioning that HDL levels do not always correlate with decreased risk of atherosclerosis, as HDL cholesterol levels can increase in cases where the reverse cholesterol transport pathway is reduced, such as SR-B1 deficiency.[5]