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J Am Soc Nephrol 11:1889-1895, 2000
© 2000 American Society of Nephrology

Role of Lipoprotein (a) and TGF-ß1 in Atherosclerosis of Hemodialysis Patients

MASAHISA FUJISAWA, REIKO HARAMAKI, HIROSHI MIYAZAKI, TSUTOMU IMAIZUMI and SEIYA OKUDA

Third Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.

Correspondence to Dr. Masahisa Fujisawa, Third Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. Phone: +81-942-31-7562; Fax: +81-942-33-6509; E-mail: fujisawa{at}med.kurume-u.ac.jp

Abstract. 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-ß1 (TGF-ß1). Plasma Lp(a) and plasma TGF-ß1 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-ß1 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-ß1 did not differ among the groups. When plasma TGF-ß1 and supernatant TGF-ß1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-ß1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-ß1 and IMT or plaque score, between mature TGF-ß1 and IMT or plaque score, or between mature TGF-ß1 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-ß1 activation in CRF patients.




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