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[Primary hypercholesterolemia: mechanisms of its development in man]
1Institute of Therapy of AMS Ukraine, Kharkov.
Insights
Hypercholesterolemia, a key risk factor for ischemic heart disease (IHD), stems from primary or secondary origins. Understanding its molecular mechanisms aids in effective lipid management and treatment strategies.
Area of Science:
- Biochemistry
- Genetics
- Cardiology
Context:
- Hypercholesterolemia is a primary risk factor for ischemic heart disease (IHD).
- It can originate from primary genetic factors or secondary causes.
- Primary hypercholesterolemia involves distinct molecular defects affecting lipid metabolism.
Purpose:
- To review the mechanisms of primary hypercholesterolemia.
- To highlight the clinical significance of understanding these mechanisms.
- To discuss current and future therapeutic approaches.
Summary:
- Discusses three main mechanisms of primary hypercholesterolemia: low LDL receptor activity, reduced LAL affinity for receptors, and apo B-lipoprotein overproduction.
- Explains how different molecular defects lead to cellular or circulating cholesterol imbalances.
- Outlines that identifying molecular defects allows for targeted combination drug therapy to normalize lipids in most patients.
Impact:
- Enables personalized treatment strategies for hypercholesterolemia based on identified molecular defects.
- Emphasizes plasmapheresis or LDL apheresis as primary treatments for homozygous familial hypercholesterolemia.
- Positions gene therapy as a promising future treatment for severe genetic forms of hypercholesterolemia.
Abstract:
The review is devoted to hypercholesterolemia which is one of the leading risk factors for IHD. By its origin it can be primary and secondary. Three major mechanisms of primary hypercholesterolemia in humans are discussed. They are: low activity of LDL receptors, reduced affinity of LAL for receptors and overproduction of lipoproteins containing apo B. Depending on mechanism nonidentical molecular defects leading to cholesterol imbalance in cells or in circulating lipoproteins are occurred. The understanding of the nature and mechanisms of hypercholesterolemia development is of great clinical value, because having determined molecular defect and using drugs combinations the majority of patients are a success to have their lipids normal. Only in the case of homozygous familial hypercholesterolemia medicamentous treatment becomes secondary and the principal therapeutic methods are plasmapheresis or selective LDL apheresis. Gene therapy as a method of homozygous familial hypercholesterolemia correction is in forthcoming future.