Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol Apolipo-protein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation

https://science.sciencemag.org/content/sci/240/4852/622.full.pdf

Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.

The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations.

A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-a-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health. It is not intended to serve as a specific guideline but will be of value to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, from which evidence-based guidelines will ensue. Topics to be addressed include epidemiology and CVD risk, ethnic and racial differences, metabolic determinants, genetic and family determinants, risk factor correlates, and effects related to nutrition, physical activity, and lipid medications.

In the United States, the National Health and …

https://www.ahajournals.org/doi/pdf/10.1161/CIR.0b013e3182160726

Triglycerides and Cardiovascular Disease A Scientific Statement From the American Heart Association

Prospective data at Framingham and elsewhere have shown conclusively that risk of coronary heart disease in persons younger than age 50 is strikingly related to the serum total cholesterol level. Within so-called normal limits risk has been found to mount over a 5-fold range. The impact has been found to be augmented by other risk factors. The contribution of the serum total cholesterol to risk has also been found to be determined by its partition in the various lipoprotein fractions. A relatively large amount of cholesterol in the low-density lipoprotein fraction is atherogenic whereas that in the high-density fraction appears protective. The independent contribution of very-low-density lipoprotein and its triglyceride or cholesterol content has on the other hand not been established. The previous position that virtually all of the lipid information pertaining to coranary heart disease resided in the serum total cholesterol must be accordingly modified. (authors)

Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study.

/pdf/triglycerides-and-cardiovascular-disease-a-scientific-25jmfgszcb.pdf

Triglycerides and Cardiovascular Disease : A Scientific Statement From the

Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components.

Lipoprotein lipase forms an enzyme-substrate complex with fat emulsions in the presence of serum lipoproteins. Lipoproteins of very low density and high density have this property, but the former are much more active per unit weight of protein. In this investigation, the activity, expressed as quantity giving half-maximal rate of production of free fatty acids, of specific glycopeptides isolated from very low density and high density lipoproteins was tested in an incubation mixture containing lipoprotein lipase from cows' milk and 1.8 mg triglyceride per ml. The two major polypeptides of high density lipoproteins were virtually inactive in amounts up to 100 µg per ml. Activity of the unfractionated apoproteins of very low density lipoprotein was similar to that of the native lipoprotein (about 4 µg/ml). Two of its polypeptides were active: one with carboxyl-terminal glutamic acid at 0.45 to 0.60µg/ml and one with carboxyl-terminal alanine at 1.8.2.8 µg/ml. Some preparations of the latter peptide were less...

Bernard Shore

Papers

Heterogeneity of human plasma very low density lipoproteins. Separation of species differing in protein components.

Role of Specific Glycopeptides of Human Serum Lipoproteins in the Activation of Lipoprotein Lipase

Isolation and characterization of polypeptides of human serum lipoproteins.

Changes in apolipoproteins and properties of rabbit very low density lipoproteins on induction of cholesteremia.

Surface exposure of apolipoproteins in high density lipoproteins. I. Reactivities with agarose-immobilized proteases.