Role of lipoprotein (a) and TGF-beta 1 in atherosclerosis of hemodialysis patients

Atherosclerotic vascular disease is a major cause of death for uremic patie nts who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of tran sforming growth factor-beta 1 (TGF-beta 1). Plasma Lp(a) and plasma TGF-bet a 1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (con trol; n = 13) were investigated. Plasma Lp(a) was significantly higher in H D (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 we re higher in HD and non-HD-CRF patients than in controls. A significant pos itive correlation was found in HD patients between Lp(a) and LMT (r = 0.377 , P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-PI significantly increased in HD (119.8 +/- 53.5 ng/ml) a nd 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-beta 1 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 signi ficant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-beta 1 and IMT o r plaque score, between mature TGF-beta 1 and LMT or plaque score, or betwe en mature TGF-beta 1 and Lp(a). In conclusion, Lp(a) may be an important at herogenic factor in CRF patients. However, it was not clarified whether Lp( a) exerts its effect by inhibiting TGF-beta 1 activation in CRF patients.