Reduced post-operative DPP4 activity associated with worse patient outcome after cardiac surgery

Noels, Heidi; Theelen, Wendy; Sternkopf, Marieke; Jankowski, Vera; Moellmann, Julia; Kraemer, Sandra; Lehrke, Michael; Märtin, Lukas; Marx, Gernot; Jankowski, Joachim; Goetzenich, Andreas; Stoppe, Christian

doi:10.1038/s41598-018-30235-w

Cited by 11 publications

(13 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Management of anesthesia and surgical procedures. Anesthesia was performed as described before regarding to our institutional routine 18 . After surgery, all patients were transferred to the intensive care unit (ICU), and the following post-operative treatment was standardized according to our institutional guidelines.…”

Section: Methodsmentioning

confidence: 99%

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Mossanen

Jansen

Pracht

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Elective cardiac surgery has low procedural complications. However, about 40% of patients develop extracardiac complications including delirium and acute kidney injury. We hypothesized that inflammatory processes and immune cell activation might be associated with these complications. We therefore prospectively included 104 patients undergoing cardiac surgery in our study. We assessed peripheral blood leukocyte populations by flow cytometry and circulating cytokines before operation, after surgery and at days one and four post-operatively. Patients undergoing cardiac surgery showed significantly elevated leukocytes and neutrophils after surgery. On the contrary, monocytes decreased after surgery and significantly increased at days 1 and 4, particularly classical (Mon1,CD14++CD16−) and intermediate (Mon2,CD14++CD16+) monocytes. While peripheral leukocyte subsets were unaltered in patients with infectious (n = 15) or cardiac complications (n = 31), post-operative leukocytes (p = 0.0016), neutrophils (p = 0.0061) and Mon2 (p = 0.0007) were clearly raised in patients developing extracardiac complications (n = 35). Using multiple logistic regression analyses, patient's age, ICU days, number of blood transfusions and elevated post-surgery Mon2 independently predicted extracardiac complications. Our findings demonstrate that elevated Mon2 after cardiac surgery are associated with an increased risk for extracardiac complications. These findings might improve the risk estimation after cardiac operations and the role of Mon2 for inflammation in cardiac surgery.Despite advances in surgical and anesthetic techniques as well as enhanced postoperative care, cardiac surgery is still associated with a high risk of postoperative complications 1 . Besides typical cardiac (e.g., arrhythmia, myocardial infarction) and infectious complications (e.g., wound infection, pneumonia and sepsis), extracardiac non-infectious complications like acute kidney injury (AKI, 30%) and delirium (up to 26-52%) are frequent in patients after cardiac surgery 2,3 . It has been speculated that a large part of these complications could be explained by excessive inflammation caused by extracorporeal cardio-pulmonary bypass (CPB), hypothermia, myocardial ischemia and reperfusion and tissue damage due to the surgical procedure 4,5 . The influence of distinct immune cells and their subpopulations on the occurrence of post-operative complications is still ambiguous and needs further investigations. Particularly monocytes seems to play in important role within this context 6,7 .Circulating monocyte subsets represent a continuum of differentiation stages 8,9 . Using the surface markers CD14 (LPS receptor) and CD16 (FcγRIII), blood monocytes can be subdivided into three subpopulations, CD14++CD16− "classical" monocytes (Mon1), CD14++CD16+ "intermediate" (Mon2) and CD14-16+

show abstract

Section: Methodsmentioning

confidence: 99%

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Mossanen

Jansen

Pracht

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…28 In addition, DPP4 can also be oxidized, which reduces its activity. 29 Dipeptidyl peptidase-4 is present on the membrane of parenchymal cells within metabolic organs, including hepatocytes, enterocytes, islets cell, and within endothelial cells and immune populations. 26,30 The level of expression depends on the cell type, differentiation state, and/or the activation state.…”

Section: Posttranscriptional Regulation Of Dpp4mentioning

confidence: 99%

Dipeptidyl Peptidase-4 at the Interface Between Inflammation and Metabolism

Trzaskalski

Fadzeyeva

Mulvihill

2020

Clin Med Insights Endocrinol Diabetes

View full text Add to dashboard Cite

Dipeptidyl peptidase-4 (DPP4) is a serine protease that rapidly inactivates the incretin peptides, glucagon-like peptide-1, and glucose-dependent insulinotropic polypeptide to modulate postprandial islet hormone secretion and glycemia. Dipeptidyl peptidase-4 also has nonglycemic effects by controlling the progression of inflammation, which may be mediated more through direct protein-protein interactions than catalytic activity in the context of nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes (T2D). Failure to resolve inflammation resulting in chronic subclinical activation of the immune system may influence the development of metabolic dysregulation. Thus, through both its cleavage and regulation of the bioactivity of peptide hormones and its influence on inflammation, DPP4 exhibits a diverse array of effects that can influence the progression of metabolic disease. Here, we highlight our current understanding of the complex biology of DPP4 at the intersection of inflammation, obesity, T2D, and NAFLD. We compare and review new mechanisms identified in basic laboratory and clinical studies, which may have therapeutic application and relevance to the pathogenesis of obesity and T2D.

show abstract

“…On the contrary, after critical limb ischemia in DDP4 deficient mice, paradoxical impairment of angiogenesis, endothelial function and circulating number of EPCs has been reported [16]. Consistent with this reduced post-operative DPP4 activity has been associated with worse patient outcome after cardiac surgery due to similar mechanism invoked during tissue ischemia [17].…”

Section: Dpp-4 Inhibitors Abstractmentioning

confidence: 88%

Is DPP4 inhibition a comrade or adversary in COVID-19 infection

Dalan

2020

Diabetes Research and Clinical Practice

View full text Add to dashboard Cite

Reduced post-operative DPP4 activity associated with worse patient outcome after cardiac surgery

Cited by 11 publications

References 59 publications

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery

Dipeptidyl Peptidase-4 at the Interface Between Inflammation and Metabolism

Is DPP4 inhibition a comrade or adversary in COVID-19 infection

Contact Info

Product

Resources

About