To the Editor: Homocysteine has an inhibitory effect on angiogenesis1. However, the vascular endothelial growth factor receptor-2 (VEGFR-2) gene has recently been found up-regulated on human atherosclerotic plaques2. In order to analyze the association between homocysteine and VEGFR-2 serum levels, we have randomly selected 26 regular hemodialysis (HD) patients ages 56
12 years (mean
SD; M = 14, F = 12), and 26 age-matched kidney transplanted individuals (KTx), ages 52
8 years (M = 21, F = 5). KTx transplant age was 13
9 months and creatinine was 1.6
0.5 mg/dL. Nine age-matched healthy volunteers (47
5 years) were also recruited. HD samples were collected at the end of the long interval period. Serum homocysteine (Hcy) and VEGFR-2 were tested by high-performance liquid chromatography (HPLC) with fluorimetric detection and a commercial enzyme-linked immunosorbent assay (ELISA) kit, respectively. Hcy was higher in HD patients (57
36
mol/L) than in KTx patients (23
8
mol/L; P < 0.001) and control patients (15
6
mol/L; P < 0.01 vs. HD; P < 0.05 vs. KTx). VEGFR-2 was lower in HD patients (1705
387 pg/mL) than in KTx patients (2449
825 pg/mL; P = 0.014) or control patients (2150
464 pg/mL) Figure 1. The present study shows that Hcy and circulating VEGFR-2 are inversely associated, consistent with previous reports showing that homocysteine inhibits angiogenesis. Our data also suggest that up-regulation of the VEGFR-2 gene is probably a local finding, and that hyperhomocysteinemia may be involved in the release of VEGFR-2 into the systemic circulation.
Figure 1.
(A) Homocysteine and (B) vascular endothelial growth factor 2 (VEGFR-2) serum levels in control, hemodialyzed (HD), and kidney transplanted (KTx) patients. *P < 0.05 vs. KTx patients; **P < 0.001 vs. KTx and control patients; #P < 0.001 vs. KTx patients and P < 0.014 vs. control patients.
Full figure and legend (15K)References
| 1. | Hajjar KA. Homocysteine: A sulph'rous fire. J Clin Invest 2001; 107: 663−664. | PubMed | ISI | ChemPort | |
| 2. | Hiltunen MO, Tuomisto TT & Niemi M et al. Changes in gene expression in atherosclerotic plaques analyzed using DNA array. Atherosclerosis 2002; 165: 23−32. | Article | PubMed | ISI | ChemPort | |


