Effect and mechanism of AGEs-induced expression of ICAM-1 and MCP-1 on rat cardiac microvascular endothelial cells
AIM: To investigate the effect and the mechanism of advanced glycation end products ( AGEs) on the expression of intercellular adhesion molecule-1 ( ICAM-1 ) and monocyte chemotatic protein-1 (MCP-1) in cultured rat cardiac microvascular endothelial cells (CMECs). METHODS: AGEs-BSA was prepared by incubating bovine serum albumin ( BSA) with high concentration of D-glucose at 37℃ in vitro. CMECs were cultured according to the descriptions in literatures. The production of ICAM-1 induced by AGEs was determined by flow cytometry (FCM) and MCP-1 was examined by enzyme-linked immunosorb-nent assay ( ELISA). Receptor for advanced glycation end products (RAGE) was detected at both protein and mRNA levels using Western blot and RT-PCR,respectively. RESULTS: AGEs (100,200 and 400 mg/L) stimulated CMECs to over-express MCP-1 [(52.5±5.5),(116.0±3.1),(139.6 ±8.7)μg /L] and ICAM-1 ( 13. 2%,14. 5%,38. 1% ) and increased the expression of RAGE at both protein and mRNA levels in a dose concentration-dependent manner (all P<0.05). CONCLUSION: AGEs up-regulates ICAM-1 and MCP-1 expressions and increases expression of RAGE in CMEC and the underlying mechanism may be that AGEs increase the expression of proinflammatory cytokines through up-regulation of RAGE. These findings further suggest that AGE-RAGE interaction is a key contributing factor leading to the development of microvascular diabetic complications.
glycosylation end products,advancedreceptor for advanced glycosylation end productsmyocardiummicrovascularendothelial cells
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