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Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease
Insights
This study investigated two sisters with severe atherosclerosis, finding extremely low high-density lipoprotein cholesterol. Low HDL cholesterol and apolipoprotein A-I levels are linked to increased atherosclerosis risk.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Genetics
Background:
- Familial hypercholesterolemia is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol.
- High-density lipoprotein (HDL) cholesterol plays a crucial role in reverse cholesterol transport and cardiovascular protection.
Observation:
- Two sisters presented with xanthomas, corneal clouding, and severe coronary atherosclerosis.
- Histological examination revealed lipid-laden histiocytes in the skin.
- Patients exhibited markedly reduced plasma concentrations of high-density lipoprotein cholesterol and apolipoprotein A-I.
Findings:
- Plasma analysis showed undetectable apolipoprotein A-I and C-III, and absent high-density lipoprotein in specific density fractions.
- Lecithin-cholesterol acyltransferase activity was significantly reduced (40% of normal).
- The metabolic half-life of infused normal high-density lipoprotein was shortened in patients.
Implications:
- These findings support the hypothesis that severely deficient high-density lipoprotein cholesterol and apolipoprotein A-I contribute to premature atherosclerosis.
- This case highlights a potential genetic basis for severe HDL deficiency and its atherogenic consequences.
- Further research into HDL metabolism and its role in preventing atherosclerosis is warranted.
Abstract:
We studied two sisters 29 and 31 years old who had skin and tendon xanthomas, corneal clouding, and severe coronary atherosclerosis. Histologic examination showed collections of lipid-laden histiocytes in the skin. The patients' plasma cholesterol concentrations were 177 and 135 mg per deciliter (4.58 and 3.49 mmol per liter). Levels of high-density-lipoprotein cholesterol were 4 and 7 mg per deciliter (0.1 and 0.2 mmol per liter). Only traces of apolipoprotein A-I were detected in whole plasma. The plasma density fraction from 1.06 to 1.21 g per milliliter contained no high-density lipoprotein on high-pressure liquid chromatography, no apolipoprotein A-I on sodium dodecyl sulfate electrophoresis, and only traces of apolipoprotein A-I on radioimmunoassay. Apolipoprotein C-III was also not detectable. The activity of lecithin-cholesterol acyltransferase was 40 per cent of normal. The half-life of infused normal high-density lipoprotein was three days (normal, 5.8 days). The parents and children of these two patients had low levels of high-density-lipoprotein cholesterol and apolipoprotein A-I. These cases support the hypothesis that low concentrations of high-density lipoprotein promote atherosclerosis.