The aim of this study was to determine the levels of regulatory peptides apelin, 
glucagon-like peptide (GLP-1) and visfatin in hypercholesterolemic and 
hyperhomocysteinemic state and to examine their relation with nitric oxide (NO) 
metabolism. 32 Male guinea pigs were divided into four groups and each group was 
fed as follows: (a) commercial chow, (b) cholesterol (chol)-rich diet, (c) 
methionine (meth)-rich diet, and (d) chol + meth-rich diet. Blood samples were 
drawn at the end of 10 weeks, and abdominal aorta was dissected for 
histopathological examination. Serum insulin, GLP-1, apelin, visfatin, and 
nitrotyrosine concentrations were measured by the manufacturer's kits based on 
ELISA; asymmetric dimethylarginine (ADMA) and arginine levels were measured by 
the high performance liquid chromatography. Homocysteine level was measured by 
the chemiluminescence immunoassay; glucose, total chol and triglyceride levels 
were measured by the autoanalyzer. The microscopic examination of aorta 
indicated varying degrees of vascular disturbance in chol- and chol + meth-fed 
groups. High levels of chol and homocysteine, accompanied with significantly low 
levels of apelin and GLP-1 were detected in the plasma. Visfatin, ADMA, and 
nitrotyrosine levels both in chol- and chol + meth-fed groups were significantly 
higher than those in control animals, whereas arginine and arginine/ADMA ratio 
were lower. This study indicated that circulating levels of apelin, GLP-1, and 
visfatin are markedly altered during the development of atherosclerotic changes 
in close association with chol, homocysteine, NO, and ADMA levels. The 
measurements of these peptides in serum may help for the diagnosis and follow-up 
of vascular dysfunction.