Association of serum lipocalin-type prostaglandin D synthase levels with subclinical atherosclerosis in untreated asymptomatic subjects.
Recent studies suggest that lipocalin-type prostaglandin (PG) D synthase (L-PGDS), which converts PGH2 to PGD2, is implicated in the pathogenesis of atherosclerosis. However, clinical evidence for the association between serum L-PGDS levels and atherosclerosis has not been reported. In this study, we measured the serum L-PGDS concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and investigated the association with traditional cardiovascular risk factors and surrogate atherosclerotic indices, such as the maximum score of the intima-media complex thickness of the carotid artery (C-IMT(max)) and the brachial-ankle pulse wave velocity (ba-PWV), in 500 non-treated asymptomatic subjects. The serum concentration of L-PGDS was 0.56+/-0.01 (mean+/-SEM, range 0.25-1.27, median 0.54) mg/L. Serum L-PGDS levels increased with age and were higher in men than in women. Serum L-PGDS was higher in subjects with hypertension and increased with increasing numbers of the traditional atherosclerotic risk factors. When the subjects were divided into four groups according to the levels of serum L-PGDS, the age-adjusted values of C-IMT(max) and ba-PWV were significantly increased in subjects with higher serum L-PGDS levels (quartile 3 and quartile 4) compared to those in the lowest quartile (quartile 1), for both genders. Multiple regression analysis including risk factors revealed that serum L-PGDS was an independent determinant for ba-PWV (beta=0.130, p<0.001). Serum L-PGDS tended to associate with C-IMT(max) but was not statistically significant (beta=0.084, p=0.075). In conclusion, our results suggest that an increase in serum L-PGDS concentration is associated with the progression of atherosclerosis.
Miwa
Yoshikazu
Y
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. ymiwa@clipharm.med.kyushu-u.ac.jp
Oda
Hiroshi
H
Shiina
Yasuhiko
Y
Shikata
Kentaro
K
Tsushima
Motoo
M
Nakano
Satomi
S
Maruyama
Taro
T
Kyotani
Shingo
S
Eguchi
Naomi
N
Urade
Yoshihiro
Y
Takahashi-Yanaga
Fumi
F
Morimoto
Sachio
S
Sasaguri
Toshiyuki
T
D001158:Arteries / Q000473:pathology; D001783:Blood Flow Velocity; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow; D012044:Regression Analysis; D012307:Risk Factors; D017678:Sex Distribution; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase