Thyroid substitution therapy induces high-density lipoprotein-associated platelet-activating factor-acetylhydrolase in patients with subclinical hypothyroidism: a potential antiatherogenic effect.
BACKGROUND
Subclinical hypothyroidism (SH) has been associated with an increased risk of ischemic heart disease, which has been partly attributed to lipid abnormalities. Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated with lipoproteins (both low-density lipoproteins [LDL], and high-density lipoproteins [HDL]). Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL.


OBJECTIVE
To evaluate qualitative changes in lipoprotein metabolism with respect to PAF-AH and PON1 activities in patients with SH before and after the restoration of euthyroidism.


METHODS
We determined the PAF-AH activity in plasma and on HDL and PON1 activities as well as the lipid profile patients with SH at baseline and after 6 months of levothyroxine substitution therapy. Thirty normolipidemic healthy individuals comprised the control group.


RESULTS
Compared to controls, patients with SH showed higher levels of total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B. Triglycerides were significantly reduced after levothyroxine treatment. Patients with SH exhibited higher plasma baseline PAF-AH activity (63.0 +/- 16.5 versus 44.3 +/- 9.5 nmol/mL per minute p < 0.0001) and lower baseline HDL associated PAF-AH (2.9 +/- 1.1 versus 3.6 +/- 0.9 nmol/mL per minute p = 0.02) compared to the control group. PON1 activities were similar in both groups. Levothyroxine treatment had no effect on plasma PAF-AH activity or PON1 activities but resulted in a significant elevation of HDL-associated PAF-AH activity (from 2.9 +/- 1.1 to 3.5 +/- 1.0 nmol/mL per minute, p = 0.003).


CONCLUSIONS
Patients with SH exhibit increased plasma PAF-AH activity and low HDL-associated PAF-AH activity. Levothyroxine induces a significant increase in HDL-PAF-AH activity. This action may represent a potential antiatherogenic effect of thyroid replacement therapy.
Milionis
Haralampos J
HJ
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
Tambaki
Afroditi P
AP
Kanioglou
Chrisa N
CN
Elisaf
Moses S
MS
Tselepis
Alexandros D
AD
Tsatsoulis
Agathocles
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000517:prevention & control*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000628:therapy*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*
D008075:Lipoproteins, HDL; D013963:Thyroid Hormones; D013972:Thyrotropin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013974:Thyroxine