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

Acta Diabetologica
Yao DaiJawahar L Mehta

Abstract

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 ≫ 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 ...Continue Reading

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Citations

Jan 17, 2016·Metabolism: Clinical and Experimental·Masashi TanakaNoriko Satoh-Asahara
Oct 17, 2015·Cardiovascular Research·Yao DaiJawahar L Mehta
Oct 18, 2015·International Journal of Cardiology·Chao-Jun YangJian Yang
Sep 27, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Robert N Mahon, Richard Hafner
Jul 22, 2016·Diabetes Care·Rena M PollackGil Leibowitz
Jan 14, 2017·Cardiovascular Drugs and Therapy·Yao DaiJawahar L Mehta
Jun 24, 2018·Pharmacological Reports : PR·Samah S AbbasHanan S El-Abhar
Nov 30, 2018·Frontiers in Physiology·Chintan N KoyaniDirk von Lewinski
Jan 11, 2019·International Journal of Endocrinology·Michishige TerasakiTsutomu Hirano
Jul 11, 2020·International Journal of Molecular Sciences·Michishige TerasakiSho-Ichi Yamagishi
Feb 3, 2021·Nature Reviews. Endocrinology·Thea N Golden, Rebecca A Simmons
Feb 12, 2021·The Journal of Clinical Endocrinology and Metabolism·Kaitlin M Love, Zhenqi Liu
May 24, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Massimiliano RuscicaCesare R Sirtori
Mar 17, 2021·Biochemical Pharmacology·R YazbeckC A Abbott
Aug 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ali AhmadiAmirhossein Sahebkar

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