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Dyslipoproteinemias

Dyslipoproteinemia

For medical students2 min readUpdated 2026-10-10

Dyslipoproteinemia is any abnormality in the blood lipoprotein profile compared to normal values. A frequent variant of this pathology is hyperlipoproteinemia, in which plasma lipoprotein concentrations increase pathologically, inevitably leading to severe vascular disorders.

Enterocyte enzymeACAT synthesizes cholesterol esters in the cells of the intestinal mucosa
Fat hydrolysisLipoprotein lipase cleaves triacylglycerols within chylomicrons in the blood
GeneticsOver 300 types of LDL receptor gene mutations have been described in hypercholesterolemia
AtherosclerosisPathological cholesterol deposition occurs in the vascular intima

Dietary Cholesterol Transport and the Role of Chylomicrons

Although virtually all types of lipoproteins participate in lipid transport, at the very first stage—the absorption of exogenous (dietary) cholesterol—chylomicrons (CMs) play the leading role. This process originates in the intestinal cells known as enterocytes.

Inside chylomicrons, cholesterol exists in two main forms:

As soon as mature chylomicrons leave the intestinal cells and enter the bloodstream, their active metabolism begins. In the blood, they are acted upon by the enzyme lipoprotein lipase (LPL). Its key task is to hydrolyze fats (triacylglycerols) that are part of the chylomicrons. As a result of this enzymatic cleavage, chylomicrons "shrink" and turn into so-called remnant chylomicrons. These remnant particles, still containing a significant amount of cholesterol, are eventually captured by liver cells—hepatocytes.

Familial Hypercholesterolemia (Type II)

Among all lipid metabolism disorders accompanied by elevated cholesterol levels, familial hypercholesterolemia is the most common disease. This is a classic example of hyperlipoproteinemia with a clear genetic etiology.

Epidemiology and Genetics: Heterozygous carriers of the defective gene occur in the population with a frequency of 1 in 500 individuals. The etiology of the disease stems from various mutations affecting the gene encoding the low-density lipoprotein (LDL) receptor protein. This gene has a very complex structure, including numerous introns and exons, resulting in a vast number of potential disruptions: over 300 types of different mutations have been described to date.

The pathogenesis of the disease develops through the following sequence:

  1. The presence of a genetic mutation leads to an alteration in the normal structure of the LDL receptor.
  2. The defective receptor loses the ability to undergo endocytosis after binding to LDL.
  3. Due to the blocked uptake of lipoproteins into cells, blood cholesterol levels rise rapidly, leading to hypercholesterolemia.
  4. Chronic plasma cholesterol excess inevitably leads to early atherosclerosis.

Biochemical Basis of Atherosclerosis

The natural and most severe outcome of long-standing dyslipoproteinemia (specifically, familial hypercholesterolemia Type II) is atherosclerosis.

From a biochemical and pathophysiological standpoint, atherosclerosis is a disease characterized by specific damage to the inner layer of the arterial wall. The key link in this process is the pathological deposition of excess cholesterol in the vascular intima. The intima (inner layer) becomes the target for lipid infiltration, which subsequently leads to vessel lumen narrowing, impaired blood flow, and severe ischemic complications.

Mnemonic

To remember where cholesterol deposits in atherosclerosis, use the association: cholesterol seeks an "intimate" relationship with the vessel, so it accumulates in the inner layer—the intima.

Frequently asked questions

What are the types of hyperlipoproteinemia according to the Fredrickson classification?

The provided sources describe the following types of hyperlipoproteinemias:

  • Type II — familial hypercholesterolemia. Characterized by elevated LDL concentrations and hypercholesterolemia due to mutations in the LDL receptor gene or apoB-100.
  • Type III — familial combined hyperlipidemia. Manifests as elevated concentrations of remnant CMs, VLDL, IDL, and LDL due to a defect in apoE structure.
  • Types IV and V — familial hypertriacylglycerolemia. Caused by overproduction of VLDL, leading to hypertriacylglycerolemia.
Which lipoproteins are responsible for the reverse transport of cholesterol from tissues to the liver?

High-density lipoproteins (HDLs) are responsible for the reverse transport of cholesterol. They function to remove excess free cholesterol from peripheral tissues, including vascular walls and macrophages, and transport it to the liver. In the liver, cholesterol is converted into bile acids or excreted in the bile. Due to this, HDLs reduce cholesterol accumulation in the vascular wall and prevent atherosclerosis, meaning they are antiatherogenic.

What role does the LCAT enzyme play in lipoprotein metabolism?

The enzyme lecithin-cholesterol acyltransferase (LCAT) is responsible for the esterification of free cholesterol on the surface of high-density lipoproteins (HDLs). Its action leads to the following results:

  • The newly formed hydrophobic cholesterol esters migrate to the core of the HDL particle.
  • Discoidal (immature) HDLs acquire a spherical shape, increase in size, and transform into HDL₃.
  • A concentration gradient is created, enabling HDLs to take up new portions of cholesterol from vascular wall macrophages and other peripheral tissues.

Thus, LCAT accelerates reverse cholesterol transport to the liver and reduces the risk of atherosclerosis.

What happens to chylomicrons after they enter the bloodstream?

In the bloodstream, they are acted upon by lipoprotein lipase, which hydrolyzes the triacylglycerols they contain. This forms remnant chylomicrons, which are taken up by hepatocytes.

Which enzyme is responsible for cholesterol ester formation in the intestine?

This process is catalyzed by the enzyme ACAT (acyl-CoA:cholesterol acyltransferase), which operates in the cells of the intestinal mucosa.

What is the pathogenesis of Type II familial hypercholesterolemia?

Mutations impair the structure of the LDL receptor, preventing it from performing endocytosis. This leads to cholesterol accumulation in the blood and the development of early atherosclerosis.

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