PMID- 31595157
OWN - NLM
STAT- MEDLINE
DCOM- 20200518
LR  - 20200518
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 15
IP  - 11
DP  - 2019
TI  - Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in 
      diabetic mice heart by regulating endothelial-mesenchymal transition.
PG  - 2393-2407
LID - 10.7150/ijbs.35736 [doi]
AB  - Cathelicidin-related antimicrobial peptide (CRAMP), antimicrobial peptide, was 
      reported to protect against myocardial ischemia/reperfusion injury. In the 
      pathology of diabetic cardiomyopathy, endothelial-to-mesenchymal transition 
      (EndMT) results from hyperglycemia-induced endothelial injury, leading to cardiac 
      fibrosis. This study aims to evaluate the effect of CRAMP on EndMT and cardiac 
      fibrosis on diabetic mice heart. Mice were subjected to streptozotocin to induce 
      diabetes. CRAMP was administered by intraperitoneal injection (1 or 8 mg/kg/d) 
      for 4 weeks from 12 weeks till 16 weeks after final streptozotocin injection. 
      Cardiac dysfunction was observed in diabetic mice. Only 8 mg/kg/d CRAMP treatment 
      proved cardiac function. Increased EndMT and fibrosis level were also observed in 
      diabetic mice heart. 8mg/kg CRAMP inhibited EndMT and fibrosis level in diabetic 
      mice. Mouse heart endothelial cells (MHECs) were treated with CRAMP and exposed 
      to high glucose. Hyperglycemia-induced EndMT in MHECs was also attenuated by 
      CRAMP treatment. Activation of TGFbeta/Smad signalling was increased in diabetic 
      mice heart tissue and hyperglycemia stimulated MHECs, which was prevented 
      following CRAMP treatment. Activation of AMPKa1/mTOR showed similar changes. 
      AMPKa1 siRNA abrogated the effects of CRAMP in MHECs. TGFbeta/Smad inhibitor 
      LY2109761 and AMPKa agonist AIRCA mimic the effect of CRAMP. In summary, CRAMP 
      can inhibit EndMT, cardiac fibrosis and protect against diabetic cardiomyopathy 
      by regulating AMPKa1/TGFbeta signalling.
CI  - (c) The author(s).
FAU - Zheng, Xiaolin
AU  - Zheng X
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Peng, Meng
AU  - Peng M
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Li, Yan
AU  - Li Y
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Wang, Xule
AU  - Wang X
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Lu, Wenjie
AU  - Lu W
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Wang, Xi
AU  - Wang X
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Shan, Yingguang
AU  - Shan Y
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Li, Ran
AU  - Li R
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Gao, Lu
AU  - Gao L
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Qiu, Chunguang
AU  - Qiu C
AD  - Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20190907
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (LY2109761)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrroles)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (AMPK alpha1 subunit, mouse)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Antimicrobial Cationic Peptides/*therapeutic use
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/drug therapy
MH  - Diabetic Cardiomyopathies/drug therapy
MH  - Echocardiography
MH  - Endothelial Cells/cytology/drug effects
MH  - Endothelium/cytology
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Fibrosis/drug therapy
MH  - Glucose/adverse effects
MH  - Hemodynamics/drug effects
MH  - Hyperglycemia/drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pyrazoles/therapeutic use
MH  - Pyrroles/therapeutic use
MH  - Signal Transduction/drug effects
MH  - Transforming Growth Factor beta/antagonists & inhibitors/metabolism
PMC - PMC6775320
OTO - NOTNLM
OT  - AMPKa1
OT  - Cathelicidin-related antimicrobial peptide
OT  - EndMT
OT  - diabetic cardiomyopathy
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2019/10/09 06:00
MHDA- 2020/05/19 06:00
PMCR- 2019/01/01
CRDT- 2019/10/10 06:00
PHST- 2019/04/14 00:00 [received]
PHST- 2019/07/25 00:00 [accepted]
PHST- 2019/10/10 06:00 [entrez]
PHST- 2019/10/09 06:00 [pubmed]
PHST- 2020/05/19 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - ijbsv15p2393 [pii]
AID - 10.7150/ijbs.35736 [doi]
PST - epublish
SO  - Int J Biol Sci. 2019 Sep 7;15(11):2393-2407. doi: 10.7150/ijbs.35736. eCollection 
      2019.