Role of Lipoprotein (a) and TGF-β1 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-β1 (TGF-β1). Plasma Lp(a) and plasma TGF-β1 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-β1 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-β1 did not differ among the groups. When plasma TGF-β1 and supernatant TGF-β1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-β1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-β1 and IMT or plaque score, between mature TGF-β1 and IMT or plaque score, or between mature TGF-β1 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-β1 activation in CRF patients.