DPP-4 inhibitors repress foam cell formation by inhibiting scavenger receptors through protein kinase C pathway

作者：Dai, Yao; Wang, Xianwei; Ding, Zufeng; Dai, Dongsheng; Mehta, Jawahar L.^*

来源：ACTA DIABETOLOGICA, 2014, 51(3): 471-478.

DOI：10.1007/s00592-013-0541-3

• DPP-4
• Foam cell formation
• LOX-1
• CD36
• PKC

Studies show that dipeptidyl peptidase-4 (DPP-4) inhibitors may have an anti-atherosclerotic effect. Since foam cells are key components of atherosclerotic plaque, we studied the effect of DPP-4 inhibitors on foam cell formation. Foam cell formation was studied by treatment of THP-1 macrophages with oxidized low-density lipoprotein in the absence or presence of DPP-4 inhibitors (sitagliptin and NVPDPP728). The expression of scavenger receptors SRA, CD36 and LOX-1 was measured, and their role in foam cell formation in the presence of DPP-4 inhibitors was examined. In additional studies, role of protein kinase C and A in the effect of DPP-4 inhibitors was examined. Foam cell formation was markedly reduced by both DPP-4 inhibitors, as was the expression of CD36 and LOX-1 (CD36 a parts per thousand << LOX-1), but not SRA. Simultaneously, there was a reduction in phosphorylated PKC, but not PKA, content. Recovery of phosphorylated PKC following treatment of cells negated the effect of DPP-4 inhibitors on foam cell formation. Further, overexpression of CD36 or LOX-1 blocked the effect of DPP-4 inhibitors on foam cell formation. DPP-4 inhibitors repress foam cell formation through the inhibition of SRs CD36 and LOX-1, most likely via the inhibition of PKC activity. This study provides novel insights into the mechanism of inhibition of atherosclerosis by DPP-4 inhibitors.

• 出版日期2014-6
• 单位新乡医学院; 安徽医科大学