Increased oxidizability of low-density lipoproteins in hypothyroidism.
Hypothyroidism leads to an increase of plasma low-density lipoprotein (LDL) cholesterol levels. Oxidation of LDL particles changes their intrinsic properties, thereby enhancing the development of atherosclerosis. T4 has three specific binding sites on apolipoprotein B; furthermore it inhibits LDL oxidation in vitro. We therefore hypothesized that T4 deficiency not only results in elevated LDL-cholesterol levels but also in increased LDL oxidation. Ten patients with overt hypothyroidism were studied when untreated (TSH 76 +/- 13 mU/L, T4 40 +/- 6 nmol/L) and again when they were euthyroid for at least 3 months during T4 treatment (TSH 2.7 +/- 0.5 mU/L, T4 115 +/- 11 nmol/L). Plasma lipids and lipoproteins and the oxidizability and chemical composition of LDL were determined. The transition from the hypothyroid to the euthyroid state was associated with a decrease (mean +/- SE) of plasma total cholesterol (5.8 +/- 0.3 vs. 4.8 +/- 0.2 mmol/L, P < 0.005), LDL cholesterol (3.8 +/- 0.3 vs. 2.9 +/- 0.2 nmol/L, P < 0.005) and apolipoprotein B (1.2 +/- 0.1 vs. 0.9 +/- 0.1 g/L, P < 0.005); plasma high-density lipoprotein cholesterol, apolipoprotein A-1, and triglycerides did not change. The actual content of dienes in LDL particles was increased in hypothyroidism, with a decrease after T4 suppletion [median (range) = 257 (165-346) vs. 188 (138-254) nmol/mg LDL protein, P < 0.005; reference range 140-180]. The lag time, an estimate of the resistance of LDL against oxidation in vitro, was shortened when hypothyroid but normalized after T4 treatment [29 (19-90) vs. 77 (42-96) min, P < 0.005; reference range 67-87]. The density, the relative fatty acid content, and the vitamin E content of LDL particles did not change. In conclusion, the hypothyroid state is not only associated with a quantitative increase of LDL particles, but it also changes their quality by increasing LDL oxidizability.
Diekman
T
T
Department of Endocrinology, University of Amsterdam, The Netherlands. w.m.wiersinga@amc.uva.nl
Demacker
P N
PN
Kastelein
J J
JJ
Stalenhoef
A F
AF
Wiersinga
W M
WM
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000188:drug therapy; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000032:analysis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use; D014284:Triiodothyronine / Q000097:blood
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014284:Triiodothyronine; D013972:Thyrotropin; D002784:Cholesterol; D013974:Thyroxine