Homocysteine transport by human aortic endothelial cells:: Identification and properties of import systems

Hyperhoniocysteinemia is an independent risk factor for cardiovascular disease. Transport Of L-homocysteine into and Out of the human vascular enclothelium is poorly understood. We hypothesized that cultured human aortic endothelial cells (HAEC) would import L-homocysteme on one or more of the L-cysteine transport systems. Inhibitors of the transporters were used to characterize the uptake of [S-35]L-homocysteine, [S-35]L-homocystine, and [S-35]L-cysteine. We found that L-homocysteine uptake is mediated by the sodium-dependent cysteine transport systems X-AG, ASC, and A.. and the sodium-independent transport system L. Thus, HAEC utilize Multiple cysteine transporters (X-AG >= L > ASC > A) to import L-homocysteine. Kinetic analysis supported the uptake results. Michaelis-Menten constants (K-m) for the four systems yielded values of 19.0, 27.1, 112, and 1000 mu M for systems L, XAG, ASC, and A, respectively. The binding and uptake of [S-35]L-homocystine, the disulfide homodimer Of L-homocysteine, was mediated by Systems XAG, L, and ASC but not by system A. In contrast to [S-35]L-homocysteine, system x(c) was active for [S-35]L-homocystine uptake. A similar pattern was observed for [S-35]L-cysteine. Thus, L-homocysteine and L-homocystine found in hyperhomocysteinemic subjects can gain entry into the vascular endothelium by way of multiple L-cysteine transporters. (c) 2005 Elsevier Inc. All rights reserved.