Short-term inhibition of DPP-4 enhances endothelial regeneration after acute arterial injury via enhanced recruitment of circulating progenitor cells

Brenner, Christoph; Kränkel, Nicolle; Kühlenthal, Sarah; Israel, Lars; Remm, Friederike; Fischer, Christian B.; Herbach, Nadja; Speer, Thimoteus; Grabmaier, Ulrich; Laskowski, Alexandra; Groß, Lisa; Theiß, Hans; Wanke, Rüdiger; Landmesser, Ulf; Franz, Wolfgang-Michael

doi:10.1016/j.ijcard.2014.09.016

Cited by 31 publications

(35 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Local SDF-1 expression has been extensively shown to be amplified in newly formed atherosclerotic lesions and predominantly be cleaved by local DPP-4 [8][9][10]21,22]. Likewise, inhibition of DPP-4 using Sitagliptin can lead to an increase in local SDF-1 concentrations as we have previously shown in various organs including the vascular system [17,23].…”

Section: Sitagliptin Inhibits Formation Of Atherosclerosis Via the Sdmentioning

confidence: 87%

DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2 macrophages

Brenner

Franz

Kühlenthal³

et al. 2015

International Journal of Cardiology

View full text Add to dashboard Cite

Section: Sitagliptin Inhibits Formation Of Atherosclerosis Via the Sdmentioning

confidence: 87%

DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2 macrophages

Brenner

Franz

Kühlenthal³

et al. 2015

International Journal of Cardiology

View full text Add to dashboard Cite

“…DPP‐4 inhibitors, such as anagliptin, inhibit the extracellular catalytic domain of DPP‐4,21 preventing the degradation of substrates including stromal cell–derived factor 122 and platelet‐activating factor 23. Soluble DPP‐4, shed from the cell surface, lacks the cytoplasmic and transmembrane domains but has preserved catalytic capacity.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase‐4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation

Ikedo

Minami

Kataoka

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundChronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP‐4 (dipeptidyl peptidase‐4) inhibitors have anti‐inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP‐4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model.Methods and Results IAs were surgically induced in 7‐week‐old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide‐treated RAW264.7 macrophages. In the anagliptin‐treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IAs, reduced the expression of MCP‐1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide‐stimulated RAW264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP‐1, and IL‐6 (interleukin 6) independent of GLP‐1 (glucagon‐like peptide 1), the key mediator in the antidiabetic effects of DPP‐4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal–regulated kinase 5), which mediates the anti‐inflammatory effects of statins, in RAW264.7 macrophages. Preadministration with an ERK5 inhibitor blocked the inhibitory effect of anagliptin on MCP‐1 and IL‐6 expression. Accordingly, the ERK5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro.ConclusionsA DPP‐4 inhibitor, anagliptin, prevents the growth of IAs via its anti‐inflammatory effects on macrophages.

show abstract

“…Recent evidence indicates a paradoxical impairment of angiogenesis, endothelial function, and circulating numbers of endothelial progenitor cells in DPP4‐deficient rats after critical limb ischemia . Moreover, sitagliptin reportedly accelerates endothelial regeneration after acute arterial injury by enhanced recruitment of circulating progenitor cells . This discrepancy may partly be because of varying DPP4 activity among different organs and tissues.…”

Section: Discussionmentioning

confidence: 99%

Combined treatment with dipeptidyl peptidase‐4 inhibitor (sitagliptin) and angiotensin‐II type 1 receptor blocker (losartan) suppresses progression in a non‐diabetic rat model of steatohepatitis

Okada

Namisaki

Moriya

et al. 2017

Hepatology Research

View full text Add to dashboard Cite

show abstract

Short-term inhibition of DPP-4 enhances endothelial regeneration after acute arterial injury via enhanced recruitment of circulating progenitor cells

Cited by 31 publications

References 49 publications

DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2 macrophages

DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2 macrophages

Dipeptidyl Peptidase‐4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation

Combined treatment with dipeptidyl peptidase‐4 inhibitor (sitagliptin) and angiotensin‐II type 1 receptor blocker (losartan) suppresses progression in a non‐diabetic rat model of steatohepatitis

Contact Info

Product

Resources

About