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The contributions of dipeptidyl peptidase IV to inflammation in heart failure.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2016 Jun 01; Vol. 310 (11), pp. H1760-72. Date of Electronic Publication: 2016 May 03. - Publication Year :
- 2016
-
Abstract
- Circulating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-α, IL-1β, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.<br /> (Copyright © 2016 the American Physiological Society.)
- Subjects :
- Animals
Biomarkers blood
Chemokine CCL2 blood
Dipeptidyl-Peptidase IV Inhibitors pharmacology
Heart physiopathology
Heart Failure blood
Heart Failure physiopathology
Inflammation blood
Inflammation physiopathology
Interleukin-1beta blood
Macrophages drug effects
Male
Rats
Rats, Wistar
Sitagliptin Phosphate pharmacology
Tumor Necrosis Factor-alpha blood
Dipeptidyl-Peptidase IV Inhibitors therapeutic use
Heart drug effects
Heart Failure drug therapy
Inflammation drug therapy
Sitagliptin Phosphate therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 310
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 27199127
- Full Text :
- https://doi.org/10.1152/ajpheart.00735.2015