COMBINED EFFECT OF INFLAMMATORY C-REACTIVE PROTEIN AND HYPERGLYCEMIA ON ENDOTHELIAL CELL DYSFUNCTION

Summary Data from literature show that endothelial dysfunct ion is a key factor in atherogenesis; it is characterized by a reduction o f the bioavailability of nitric oxide (NO), whereas endothelium-derived contracting factors are increased leading to an impairment of endothelium-dependent vasodilation. The main causes of NO reduced bioavailability are its interaction with reactive o xygen species leading to reactive nitrogen species (RNS) formation, and the decreased capacity of endothelial nitric oxide synthase (eNOS) to produce NO. Inflammation is another end-result of endothelial dysfunction. Our aim was to evaluate the effect of C-reactive pr otein (CRP), known marker of inflammation, on NO bioavailability and endothelial -derived inflammatory molecules. To this purpose, we prepared pure CRP and incubated it with human umbilical vein endothelial cells (HEC) in DMEM with 5 mM or 25 mM glucose. We determined the expression of eNOS, the levels of NO and intracellu lar RNS. Results showed that CRP inhibits the gene and protein expression of eNOS an d NO production, determines intracellular accumulation of RNS and up regulation of MCP-1 expression. We demonstrated that the signalling pathways activated by CRP in HEC were p38MAPK and NF-kB dependent. Addition of 25 mM glucose in the culture medium aggravates this process. In conclusion, CRP combined with hyperglycemia may contribute to accelerated atherosclerosis in diabetes by inducing endothelial cell dysfunction.