ROLE OF LIPOPROTEIN-BOUND NEFAS IN ENHANCING THE SPECIFIC ACTIVITY OFPLASMA CETP IN THE NEPHROTIC SYNDROME

Plasma cholesteryl ester transfer protein (CETP) activity, evaluated b y the transfer of radiolabeled cholesteryl esters from a tracer dose o f tritiated HDL to the plasma apolipoprotein B-containing lipoproteins , was significantly higher in patients with untreated idiopathic nephr otic syndrome (n = 15) than in normolipidemic control subjects (n = 22 ) (81.5 +/- 8.4 versus 43.1 +/- 3.1 mu g CE.mL(-1).h(-1), respectively ; P < .001). The increased CETP activity in nephrotic plasma was expla ined by a significant rise in both the CETP mass concentration (3.2 +/ - 0.2 versus 2.1 +/- 0.1 mg/L; P < .001), and the specific CETP activi ty, calculated as the ratio of CETP activity to CETP mass (25.3 +/- 1. 7 versus 20.4 +/- 1.6 mu g CE.mg(-1).h(-1); P < .05). Elevated CETP ac tivity in nephrotic patients was shown to be associated with a signifi cant decrease in the mean size of LDL (24.4 +/- 0.5 versus 26.3 +/- 0. 5 nm; P < .0001) as well as in the relative abundance of HDL2a (29.6 /- 1.6% versus 34.8 +/- 1.1%; P < .05). The nephrotic syndrome was cha racterized by a significant increase in the relative proportion of lip oprotein-bound nonesterified fatty acids (NEFAs) (35.4 +/- 7.7% versus 7.6 +/- 3.0% of total; P < .01), leading to a significant increase in the electronegative charge of LDL (-4.3 +/- 0.1 versus -3.9 +/- 0.1 m V; P < .05) and HDL (-11.5 +/- 0.1 versus -11.1 +/- 0.2 mV; P < .05). Compared with native, nonsupplemented plasma, removal of lipoprotein-b ound NEFAs by addition of fatty acid-poor albumin to total plasma from nephrotic patients or control subjects significantly decreased CETP a ctivity and specific CETP activity. Specific CETP activity no longer d iffered between nephrotic and control groups after albumin supplementa tion (19.7 +/- 1.5 versus 17.7 +/- 1.5 mu g CE.mg(-1).h(-1); NS). It i s concluded that, in addition to elevated CETP mass concentration, lip oprotein-bound NEFAs, by increasing the negative electrostatic charge of nephrotic lipoproteins, can facilitate the CETP-mediated neutral-li pid transfer reaction in total plasma from nephrotic patients.