EFFECT OF GLYCATION ON THE PROPERTIES OF LIPOPROTEIN(A)

Lipoprotein(a) [Lp(a)] was glycated by incubation in vitro with glucos e (0 to 200 mmol/L), and its properties were compared with native Lp(a ) and native and glycated LDL. Glucose was incorporated into Lp(a) in proportions that mirrored the distribution of lysines between apolipop rotein (apo) B-100 and apo(a). Because the kringle IV domains of apo(a ) are lysine poor, only 10% of glucose bound to apo(a), whereas 90% wa s attached to the apoB-100 of Lp(a). Approximately 3% of the lysines o f both Lp(a) and LDL were modified, which is a level comparable with t hat observed in LDL isolated from diabetic individuals. Glucose uptake by Lp(a) and LDL was almost identical and was linear as a function of concentration and time. Glycation increased the negative charge of Lp (a) and LDL as monitored by electrophoresis and ion-exchange chromatog raphy and also reduced the affinity of Lp(a) and LDL for heparin-Sepha rose. Glycation did not affect the lysine-binding property of Lp(a) or generate measurable malondialdehyde oxidation adducts. The catabolism of glycated Lp(a) by human monocyte-derived macrophages (HMDMs), like that of native Lp(a), was largely LDL receptor independent. Both glyc ated Lp(a) and LDL were degraded at a comparatively faster rate and st imulated greater cholesteryl ester formation than their unmodified cou nterparts. However, the degradation rate of glycated Lp(a) was approxi mately four- to fivefold slower and its stimulation of cholesteryl est er formation was ninefold lower than that of either form of LDL. These results show that Lp(a) can be glycated nonenzymatically in vitro, th at the incorporation of glucose is dependent on the distribution of ly sines between apo(a) and apoB-100, and that glycation does not affect the lysine-binding properties of Lp(a). Furthermore, glycation produce d modest increases in the degradation rate of Lp(a) and associated cho lesteryl ester synthesis by HMDMs. Based on these data, glycation does not appear to significantly enhance the atherogenic potential of unmo dified Lp(a).