BACKGROUND: Initiation of an atherosclerotic lesion requires endothelial expression of adhesion molecules. Selenium (Se), a biologically essential trace element, can inhibit cytokine (e.g., TNF-alpha)-induced expression of adhesion molecules. Atherosclerosis is accelerated in diabetic patients. This is at least partially caused by hyperglycemia and hyperinsulinemia increasing adhesion molecule expression. These experiments tested whether Se can also alter high glucose- and high insulin-induced expression of adhesion molecules. METHODS: Human umbilical vein endothelial cells (HUVECs) were pretreated with Se and stimulated by high glucose or high insulin. Expression of adhesion molecules was measured by Western blot. RESULTS: Se (100 nmol/L) significantly inhibited glucose (25 mmol/L)-induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. Moreover, Se significantly inhibited insulin (100 nmol/L)-induced VCAM-1 and ICAM-1 expression, whereas high insulin had no inducing effect on E-selectin. Se also inhibited high glucose- and high insulin-induced activation of p38 mitogen-activated protein kinase (p38), which indicated that the preventive effects of Se on adhesion molecules may be associated with p38. The important role of p38 in Se effects was further confirmed using p38 inhibitor SB203580. CONCLUSIONS: These results suggest that Se can inhibit high glucose- and high insulin-induced expression of adhesion molecules. Such antagonism is at least partially mediated through the modulation of p38 pathway. Therefore, Se may be considered as a potential preventive intervention for diabetes-accelerated atherosclerosis.
BACKGROUND: Initiation of an atherosclerotic lesion requires endothelial expression of adhesion molecules. Selenium (Se), a biologically essential trace element, can inhibit cytokine (e.g., TNF-alpha)-induced expression of adhesion molecules. Atherosclerosis is accelerated in diabeticpatients. This is at least partially caused by hyperglycemia and hyperinsulinemia increasing adhesion molecule expression. These experiments tested whether Se can also alter high glucose- and high insulin-induced expression of adhesion molecules. METHODS:Human umbilical vein endothelial cells (HUVECs) were pretreated with Se and stimulated by high glucose or high insulin. Expression of adhesion molecules was measured by Western blot. RESULTS:Se (100 nmol/L) significantly inhibited glucose (25 mmol/L)-induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. Moreover, Se significantly inhibited insulin (100 nmol/L)-induced VCAM-1 and ICAM-1 expression, whereas high insulin had no inducing effect on E-selectin. Se also inhibited high glucose- and high insulin-induced activation of p38 mitogen-activated protein kinase (p38), which indicated that the preventive effects of Se on adhesion molecules may be associated with p38. The important role of p38 in Se effects was further confirmed using p38 inhibitor SB203580. CONCLUSIONS: These results suggest that Se can inhibit high glucose- and high insulin-induced expression of adhesion molecules. Such antagonism is at least partially mediated through the modulation of p38 pathway. Therefore, Se may be considered as a potential preventive intervention for diabetes-accelerated atherosclerosis.
Authors: Eric M Cockman; Vivek Narayan; Belinda Willard; Sumangala P Shetty; Paul R Copeland; Donna M Driscoll Journal: RNA Biol Date: 2019-08-21 Impact factor: 4.652