Role of lipoprotein (a) and TGF-beta 1 in atherosclerosis of hemodialysis patients.
Atherosclerotic vascular disease is a major cause of death for uremic patients who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming growth factor-beta 1 (TGF-beta 1). Plasma Lp(a) and plasma TGF-beta 1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were investigated. Plasma Lp(a) was significantly higher in HD (18.75 +/- 1.62 mg/ml) and non-HD-CRF patients (25.0 +/- 8.4 mg/ml) than in control subjects (10.9 +/- 5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by measuring the intima-media thickness (IMT) and plaque score with the use of an ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF patients than in controls. A significant positive correlation was found in HD patients between Lp(a) and IMT (r = 0. 377, P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-beta 1 significantly increased in HD (119.8 +/- 53.5 ng/ml) and non-HD-CRF patients (93.2 +/- 25.0 ng/ml) compared with control subjects (17.7 +/- 6.4 ng/ml), whereas the plasma level of mature (active) TGF-beta1 did not differ among the groups. When plasma TGF-beta 1 and supernatant TGF-beta 1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-beta 1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-beta 1 and IMT or plaque score, between mature TGF-beta 1 and IMT or plaque score, or between mature TGF-beta 1 and Lp(a). In conclusion, Lp(a) may be an important atherogenic factor in CRF patients. However, it was not clarified whether Lp(a) exerts its effect by inhibiting TGF-beta 1 activation in CRF patients.
Fujisawa
Masahisa
M
Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Haramaki
Reiko
R
Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Miyazaki
Hiroshi
H
Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Imaizumi
Tsutomu
T
Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
Okuda
Seiya
S
Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.
D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
D008055:Lipids; D017270:Lipoprotein(a); C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1