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[Atherosclerosis in familial hypercholesteremia possibly induced by defective HDL]
Insights
Familial hypercholesterolemia (FH) is linked to altered lipoprotein composition, specifically lower protein in LDL and increased apo-A II and apo-D in HDL2. These changes in high-density lipoproteins (HDL) may impact their protective role against atherosclerosis.
Area of Science:
- Lipid metabolism
- Cardiovascular disease research
- Biochemistry
Context:
- Familial hypercholesterolemia (FH) is characterized by elevated, atherogenic low-density lipoproteins (LDL) due to LDL-receptor defects.
- High-density lipoproteins (HDL) are generally protective against atherosclerosis but are understudied in FH.
- HDL2's role in cholesterol removal requires further investigation in the context of FH.
Purpose:
- To compare lipoprotein composition and apolipoprotein profiles in patients with familial hypercholesterolemia (FH) and healthy controls.
- To investigate potential alterations in HDL2 and HDL3 in FH patients.
- To explore the relationship between FH, LDL, and HDL subspecies.
Summary:
- Patients with FH exhibited significantly lower protein content in LDL compared to controls (p < 0.01).
- HDL2 from FH patients showed significantly higher percentages of apolipoprotein A-II (apo-A II) and apolipoprotein D (apo-D) (p < 0.01).
- HDL3 from FH patients contained significantly less apolipoprotein E (apo-E) (p < 0.02).
Impact:
- Findings suggest altered apolipoprotein composition in HDL subspecies in FH, potentially affecting their atheroprotective functions.
- This study provides new insights into the complex lipid abnormalities in FH beyond LDL elevation.
- Further research is warranted to elucidate the functional consequences of these compositional changes on atherosclerosis development.
Abstract:
The distinct increase in the highly atherogenic plasma low-density lipoproteins (LDL) caused by the wellknown LDL-receptor defect is considered to be responsible for the development of atherosclerosis in familial hypercholesterolemia (FH). In contrast to the atherogenic LDL, the high-density lipoproteins (HDL) are considered to have a protective effect against the development of atherosclerosis and have hitherto been insufficiently investigated in association with FH. HDL2 are assumed to be important in the removal of free cholesterol from the peripheral tissue to the liver, but this hypothesis needs to be supported by further experimental investigations. In this study 18 patients (7 men/11 women) with familial hypercholesterolemia (FH) were compared with 18 healthy controls (8 men/10 women). From fasting plasma the following parameters were determined: cholesterol, triglycerides, phospholipids, HDL-cholesterol, by rate zonal ultracentrifugation the lipoproteins VLDL (very low-density lipoproteins), IDL (intermediate-density lipoproteins), LDL (low-density lipoproteins), HDL2 and HDL3, as well as the activities of lipoprotein lipase (LPL) and hepatic lipase (HTGL). In addition, the percentage composition of the major apolipoproteins (apo) of HDL2 and HDL3 were determined by polyacrylamide disc-gel electrophoresis. In LDL of patients with FH the percentage amount of protein was significantly (p less than 0.01) smaller than in controls. Furthermore, in HDL2 of patients with FH, the percentage content of apo-A II and apo-D was significantly (both p less than 0.01) higher than in controls. In HDL3 of patients with FH a significantly smaller (p less than 0.02) amount of apo-E was revealed than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)