PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Inhibiting DPP4 in a mouse model of HHT1 results in a shift towards regenerative macrophages and reduces fibrosis after myocardial infarction.

Abstract Hereditary Hemorrhagic Telangiectasia type-1 (HHT1) is a genetic vascular disorder caused by haploinsufficiency of the TGFβ co-receptor endoglin. Dysfunctional homing of HHT1 mononuclear cells (MNCs) towards the infarcted myocardium hampers cardiac recovery. HHT1-MNCs have elevated expression of dipeptidyl peptidase-4 (DPP4/CD26), which inhibits recruitment of CXCR4-expressing MNCs by inactivation of stromal cell-derived factor 1 (SDF1). We hypothesize that inhibiting DPP4 will restore homing of HHT1-MNCs to the infarcted heart and improve cardiac recovery.
PMID
Related Publications

Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia.

DPP4 Inhibition Ameliorates Cardiac Function by Blocking the Cleavage of HMGB1 in Diabetic Mice After Myocardial Infarction.

Endoglin has a crucial role in blood cell-mediated vascular repair.

Mononuclear cells and vascular repair in HHT.

Impaired recruitment of HHT-1 mononuclear cells to the ischaemic heart is due to an altered CXCR4/CD26 balance.

Authors

Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 29253907
OWN - NLM
STAT- In-Process
LR  - 20171224
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 12
DP  - 2017
TI  - Inhibiting DPP4 in a mouse model of HHT1 results in a shift towards regenerative 
      macrophages and reduces fibrosis after myocardial infarction.
PG  - e0189805
LID - 10.1371/journal.pone.0189805 [doi]
AB  - AIMS: Hereditary Hemorrhagic Telangiectasia type-1 (HHT1) is a genetic vascular
      disorder caused by haploinsufficiency of the TGFbeta co-receptor endoglin.
      Dysfunctional homing of HHT1 mononuclear cells (MNCs) towards the infarcted
      myocardium hampers cardiac recovery. HHT1-MNCs have elevated expression of
      dipeptidyl peptidase-4 (DPP4/CD26), which inhibits recruitment of
      CXCR4-expressing MNCs by inactivation of stromal cell-derived factor 1 (SDF1). We
      hypothesize that inhibiting DPP4 will restore homing of HHT1-MNCs to the
      infarcted heart and improve cardiac recovery. METHODS AND RESULTS: After inducing
      myocardial infarction (MI), wild type (WT) and endoglin heterozygous (Eng+/-)
      mice were treated for 5 days with the DPP4 inhibitor Diprotin A (DipA). DipA
      increased the number of CXCR4+ MNCs residing in the infarcted Eng+/- hearts
      (Eng+/- 73.17+/-12.67 vs. Eng+/- treated 157.00+/-11.61, P = 0.0003) and
      significantly reduced infarct size (Eng+/- 46.60+/-9.33% vs. Eng+/- treated
      27.02+/-3.04%, P = 0.03). Echocardiography demonstrated that DipA treatment
      slightly deteriorated heart function in Eng+/- mice. An increased number of
      capillaries (Eng+/- 61.63+/-1.43 vs. Eng+/- treated 74.30+/-1.74, P = 0.001) were
      detected in the infarct border zone whereas the number of arteries was reduced
      (Eng+/- 11.88+/-0.63 vs. Eng+/- treated 6.38+/-0.97, P = 0.003). Interestingly,
      while less M2 regenerative macrophages were present in Eng+/- hearts prior to
      DipA treatment, (WT 29.88+/-1.52% vs. Eng+/- 12.34+/-1.64%, P<0.0001), DPP4
      inhibition restored the number of M2 macrophages to wild type levels.
      CONCLUSIONS: In this study, we demonstrate that systemic DPP4 inhibition restores
      the impaired MNC homing in Eng+/- animals post-MI, and enhances cardiac repair,
      which might be explained by restoring the balance between the inflammatory and
      regenerative macrophages present in the heart.
FAU - Dingenouts, Calinda K E
AU  - Dingenouts CKE
AUID- ORCID: http://orcid.org/0000-0003-3889-9907
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Bakker, Wineke
AU  - Bakker W
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Lodder, Kirsten
AU  - Lodder K
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Wiesmeijer, Karien C
AU  - Wiesmeijer KC
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Moerkamp, Asja T
AU  - Moerkamp AT
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Maring, Janita A
AU  - Maring JA
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Arthur, Helen M
AU  - Arthur HM
AD  - Institute of Genetic Medicine, Newcastle University, International Centre for
      Life, Newcastle upon Tyne, United Kingdom.
FAU - Smits, Anke M
AU  - Smits AM
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
FAU - Goumans, Marie-Jose
AU  - Goumans MJ
AD  - Department of Molecular Cell Biology, Leiden University Medical Center, Leiden,
      the Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20171218
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
PMC - PMC5734765
EDAT- 2017/12/19 06:00
MHDA- 2017/12/19 06:00
CRDT- 2017/12/19 06:00
PHST- 2017/04/12 00:00 [received]
PHST- 2017/12/02 00:00 [accepted]
PHST- 2017/12/19 06:00 [entrez]
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2017/12/19 06:00 [medline]
AID - 10.1371/journal.pone.0189805 [doi]
AID - PONE-D-17-13309 [pii]
PST - epublish
SO  - PLoS One. 2017 Dec 18;12(12):e0189805. doi: 10.1371/journal.pone.0189805.
      eCollection 2017.