Aims
Glibenclamide, a diabetes mellitus type 2 medication, has anti-inflammatory and autoimmune properties. This study investigated the effects of glibenclamide on transplant-induced arteriosclerosis as well as the underlying molecular events.
Conclusion
Glibenclamide protected against aorta transplantation-induced arteriosclerosis by reducing inflammatory factors in vivo and inhibited macrophage migration and MCP-1 production in vitro.
Methods
Male C57Bl/6 (H-2b) and BALB/c (H-2d) mice were used for aorta transplantation. We used hematoxylin and eosin (HE) and Elastic Van Gieson (EVG) staining for histological assessment, and qRT-PCR and ELISA to measure mRNA and protein levels. Mouse peritoneal macrophages were isolated for lipopolysaccharide (LPS) stimulation and glibenclamide treatment followed by ELISA, Western blot, and Transwell assays.
Results
Glibenclamide inhibited transplant-induced arteriosclerosis in vivo. Morphologically, glibenclamide reduced inflammatory cell accumulation and collagen deposition in the aortas. At the gene level, glibenclamide suppressed aortic cytokine mRNA levels, including interleukin-1β (IL-1β; 10.64 ± 3.19 vs. 23.77 ± 5.72; P < .05), tumor necrosis factor-α (TNF-α; 4.59 ± 0.78 vs. 13.89 ± 5.42; P < .05), and monocyte chemoattractant protein-1 (MCP-1; 202.66 ± 23.44 vs. 1172.73 ± 208.80; P < .01), while IL-1β, TNF-α, and MCP-1 levels were also reduced in the mouse sera two weeks after glibenclamide treatment (IL-1β, 39.40 ± 13.56 ng/ml vs. 78.96 ± 9.39 ng/ml; P < .01; TNF-α, 52.60 ± 13.00 ng/ml vs. 159.73 ± 6.76 ng/ml; P < .01; and MCP-1, 56.60 ± 9.07 ng/ml vs. 223.07 ± 36.28 ng/ml; P < .001). Furthermore, glibenclamide inhibited macrophage expression and secretion of inflammatory factors in vitro through suppressing activation of the nuclear factor-κB (NF-κB) pathway and MCP-1 production.