Abstract
Elevated plasma homocysteine is connected to atherosclerosis and increased cerebrovascular and ischemic heart disease especially in the patients with type 2 diabetes. Effects of metformin (10 μg mL −1 ), insulin (1 mUI mL −1 ), and their combination administration in condition of mild hyperhomocysteinemia (30 μmol dm −3 ) and hyperglycemia (12 mmol dm −3 ) on human aortic endothelial cells (HAEC) was investigated. HAEC were cultured 4 h in a medium with homocysteine (7 and 30 μmol dm −3 ) and glucose (5.5 and 12.0 mmol dm −3 ). E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) expressions were analysed by flow-cytometry. Controls were CAMs expression on HAEC in medium with physiological concentration of homocysteine and glucose. HAEC, incubated additionally with 30 μmol dm −3 homocysteine, increased expression of ICAM-1 for 65 % (p = 0.07) and decreased of E-selectin for 30 % (p = 0.07) and VCAM-1 for 13 % (0.06). In condition of mild hyperhomocysteinemia and hyperglycemia there was a statistically significant increase of ICAM- 1 expression (for 22 %, p = 0.04), while administration of metformin and insulin did not statistically sig- nificantly influence adhesion molecules expression. Observed significant overexpression of ICAM-1, leads us to conclude that combination of mild hyperhomocisteinemia and hyperglycemia could have sig- nificant influence on development of inflammation and atherosclerosis in diabetic patients.(doi: 10.5562/cca1810)
Highlights
Homocysteine (Hcy) is sulfhydryl amino acid metabolite of dietary methionine
The expression of intercellular adhesion molecule-1 (ICAM-1) was statistically significant increased for 22 % (p = 0.04), while the expression of E-selectin was reduced for 29.7 % (p = 0.32) and vascular adhesion molecule-1 (VCAM-1) was decreased by 69 % (p = 0.22) on human aortic endothelial cells (HAEC) incubated in this medium compared to expression in control medium
Numerous in vivo studies showed that hyperhomocysteinemia provokes endothelial dysfunction increased by oxidative stress[30,31] and decreases discharge of NO causing increase of vasodilatation.[32−34] elevated Hcy in plasma is connected to increased lipid peroxidation and production of reactive oxygen species (ROS),[35−37] which testify its thrombogenic activity and eventually disorder in the coagulation system.[38−41] Silverman et al showed that elevated Hcy in culture of human aortic endothelial cells after 24 h of incubation increases expression of VCAM-1 and adhesion of monocytes to the endothelial cells surface
Summary
Homocysteine (Hcy) is sulfhydryl amino acid metabolite of dietary methionine. Elevated plasma Hcy is one of independent cardiovascular risk factors. It is connected to accelerated atherosclerosis and increased cerebrovascular and ischemic heart disease.[1] Further, more often Hcy levels are elevated modestly in the general population. These are strong predictors of existent and future development of vascular pathologies.[2]. Magnified plasma level of Hcy seems to contribute to cardiovascular disease, in part, by inducing endothelial cell (EC) dysfunction. Moderately elevated Hcy causes EC damage and exacerbates hypertension-related atherosclerosis,[3] and impairs flowmediated arterial dilation.[4] elevated plasma Hcy level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus.[5] In vitro, Hcy increases leukocyte adhesion to cultured endothelial cells,[6] and upregulates vascular cell adhesion molecule-1 expression in cultured HAEC and enhances monocyte adhesion.[7]
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