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Hyperthyroidism influences the distribution and apolipoprotein A composition of the high density lipoproteins in man
Insights
Hyperthyroidism significantly alters high density lipoprotein (HDL) metabolism, decreasing HDL cholesterol and apolipoprotein A-I levels, particularly in the HDL2b subclass. Treatment reverses these changes, highlighting thyroid hormones
Area of Science:
- Endocrinology
- Lipid Metabolism
- Cardiovascular Research
Background:
- Hyperthyroidism is known to affect lipid profiles.
- Previous studies indicate alterations in high-density lipoprotein (HDL) components.
- The specific impact on HDL subclasses and apolipoprotein composition requires detailed investigation.
Purpose of the Study:
- To characterize hyperthyroidism-induced alterations in HDL distribution and composition.
- To investigate changes in HDL subclasses, including HDL2b.
- To analyze the impact on apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) within HDL particles.
Main Methods:
- Studied 11 hyperthyroid women before and during treatment.
- Analyzed plasma concentrations of lipids and apolipoproteins.
- Utilized isopycnic ultracentrifugation to separate lipoprotein subclasses.
- Employed immunological procedures and polyacrylamide gradient gel electrophoresis for detailed particle analysis.
Main Results:
- Hyperthyroidism decreased total cholesterol, HDL cholesterol, phospholipids, apo A-I, and apo B.
- Significant reduction observed in the HDL2b fraction, with lower cholesterol, phospholipids, and apo A-I.
- Hyperthyroidism altered HDL2b apo A composition, decreasing the apo A-I to apo A-II ratio, primarily by reducing (A-I)HDL particles.
Conclusions:
- Hyperthyroidism significantly impacts HDL metabolism, affecting HDL subclasses and apolipoprotein composition.
- Thyroid hormones are crucial regulators of HDL metabolism, influencing apo A-I concentration and distribution.
- Treatment effectively reverses the detrimental effects of hyperthyroidism on HDL composition.
Abstract:
Hyperthyroidism has a different influence on the major high density lipoprotein (HDL) components cholesterol, apoprotein (apo) A-I, and apo A-II. To characterize in greater detail the alterations induced by hyperthyroidism within the HDL subclasses, we investigated HDL distribution and composition in 11 hyperthyroid women before and during treatment. The plasma concentrations of total cholesterol, HDL cholesterol, phospholipids, apo A-I, and apo B were decreased when the patients were hyperthyroid compared with the values during treatment. Apo A-II and apo C-III levels were only slightly lower in the hyperthyroid state. Triglyceride and apo E concentrations did not change significantly during therapy. Analysis of lipoprotein subclasses separated by isopycnic ultracentrifugation revealed 1) marked decreases in low density lipoprotein (LDL) cholesterol, phospholipids, and apo B; 2) less pronounced reductions in the very low density lipoprotein (VLDL) lipid and apo B concentrations; and 3) a consistent decrease in the HDL2b (density, 1.063-1.100 g/ml) fraction in the hyperthyroid patients. The reduction in HDL2b mass was associated with lower concentrations of HDL2b cholesterol, phospholipids, and apo A-I. The HDL2b apo A-II levels remained constant during treatment. Hyperthyroidism, therefore, modified the apo A composition of the HDL2b particles and resulted in a decreased molar apo A-I to apo A-II ratio within HDL2b. Further analysis of HDL particles differing in their apo A composition; i.e. HDL particles containing apo A-I only [(A-I)HDL] or containing both apo A-I and A-II [(A-I + A-II)HDL], by immunological procedures suggested that hyperthyroidism influenced the apo A content of HDL2b mainly by changing the proportions of (A-I)HDL and (A-I + A-II)HDL and the amount of apo A-I associated with (A-I)HDL. Treatment reversed the preferential decrease in (A-I)HDL within the HDL2b subclass. The particle sizes within HDL subfractions, measured by polyacrylamide gradient gel electrophoresis, were similar in the untreated and treated patients. Consequently, the decreased mass of apo A-I and lipids within HDL2b in the hyperthyroid patients could be attributed to a reduced number of identically sized particles within this fraction. These data demonstrate that the thyroid hormones are important regulators of HDL metabolism through their influence on the concentration and distribution of apo A-I.