Browse the corpus

Lipoproteins are lipid transport molecules that transport plasma lipids. Specific lipoproteins are risk factors for cardiovascular disease and other metabolic diseases. Understanding lipoproteins and the different ways in which to manipulate their metabolism is an essential step towards preventing disease and morbidity in the general population. This topic highlights the cellular and molecular functions of lipoprotein metabolism, its utility in diagnostic testing, its role in disease pathology, and its clinical significance.

LDL-cholesterol is a leading cause of atherosclerotic cardiovascular disease (ASCVD); this involves many processes that ultimately result in ASCVD. LDL accumulates in circulating macrophages following modifications, such as oxidation. Oxidized LDL acts as a chemoattractant for monocytes, which then differentiate into macrophages. These macrophages become trapped in the vessel wall, likely due to abnormal endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1.[11] The LDL particle promotes an inflammatory response, leading to increased cytokine and antibody levels. The modified LDL in macrophages, now called foam cells, has the potential to rupture, releasing oxidized LDL, enzymes, and free radicals that can further damage the vessel wall.[12] Additionally, the modified LDL impairs nitric oxide release due to dysfunctional endothelial function. This process reduces the vessel’s ability to vasodilate appropriately. Lastly, oxidized LDL causes increased platelet aggregation and thromboxane release. The net result is that platelet activity and aggregation become enhanced.[13] Triglyceride-rich HDL also carries implications for ASCVD, as it reduces macrophage efflux capacity, promotes monocyte infiltration into the arterial wall, and increases expression of pro-inflammatory genes. Apolipoprotein C-III, which inhibits LPL, may also promote atherosclerosis by resulting in elevated triglyceride-rich lipoproteins. Studies have found that lower C-III is associated with lower triglyceride levels and reduced risk for ASCVD.[14] IDL may also be a predictive measurement of ASCVD, and in patients with normal total cholesterol but an elevated IDL/HDL ratio, there is a significantly increased risk for ASCVD.[15] Apo B-100 is directly related to the LDL particle number. When ApoB-100 lipoproteins are elevated, the risk of atherosclerosis increases, even in the absence of other risk factors. Some propose that atherogenesis is due to the subendothelial retention of apo B-100 by proteoglycans in the extracellular matrix.[16]