PMID- 30312306
OWN - NLM
STAT- MEDLINE
DCOM- 20190311
LR  - 20190311
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 10
DP  - 2018
TI  - Cardiac leptin overexpression in the context of acute MI and reperfusion 
      potentiates myocardial remodeling and left ventricular dysfunction.
PG  - e0203902
LID - 10.1371/journal.pone.0203902 [doi]
LID - e0203902
AB  - BACKGROUND: Acute MI induces leptin expression in the heart, however the role of 
      myocardial leptin in cardiac ischemia and reperfusion (IR) remains unknown. To 
      shed light on the effects of elevated levels of leptin in the myocardium, we 
      overexpressed cardiac leptin and assessed local remodeling and myocardial 
      function in this context. METHODS AND RESULTS: Cardiac leptin overexpression was 
      stimulated in mice undergoing IR by a single intraperitoneal injection of leptin 
      antagonist (LepA). All mice exhibited a normal pattern of body weight gain. A 
      rapid, long-term upregulation of leptin mRNA was demonstrated in the heart, 
      adipose, and liver tissues in IR/LepA-treated mice. Overexpressed cardiac leptin 
      mRNA extended beyond postoperative day (POD) 30. Plasma leptin peaked 7.5 hours 
      postoperatively, especially in IR/LepA-treated mice, subsiding to normal levels 
      by 24 hours. On POD-30 IR/LepA-treated mice demonstrated cardiomyocyte 
      hypertrophy and perivascular fibrosis compared to IR/saline controls. 
      Echocardiography on POD-30 demonstrated eccentric hypertrophy and systolic 
      dysfunction in IR/LepA. We recorded reductions in Ejection Fraction (p<0.001), 
      Fraction Shortening (p<0.01), and Endocardial Fraction Area Change (p<0.01), and 
      an increase in Endocardial Area Change (p<0.01). Myocardial remodeling in the 
      context of IR and cardiac leptin overexpression was associated with increased 
      cardiac TGFbeta ligand expression, activated Smad2, and downregulation of STAT3 
      activity. CONCLUSIONS: Cardiac IR coinciding with increased myocardial leptin 
      synthesis promotes cardiomyocyte hypertrophy and fibrosis and potentiates 
      myocardial dysfunction. Plasma leptin levels do not reflect cardiac leptin 
      synthesis, and may not predict leptin-related cardiovascular morbidity. Targeting 
      cardiac leptin is a potential treatment for cardiac IR damage.
FAU - Kain, David
AU  - Kain D
AD  - Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel.
FAU - Simon, Amos J
AU  - Simon AJ
AD  - Cancer Research and Institute of Hematology, Sheba Medical Center, Sackler 
      Faculty of Medicine, Tel Aviv University, Israel.
FAU - Greenberg, Avraham
AU  - Greenberg A
AD  - Department of Developmental Biology and Cancer Research, The institute for 
      Medical Research Israel-Canada, The Hebrew University-Hadassah medical School, 
      Jerusalem, Israel.
FAU - Ben Zvi, Danny
AU  - Ben Zvi D
AUID- ORCID: 0000-0002-8697-9744
AD  - Department of Developmental Biology and Cancer Research, The institute for 
      Medical Research Israel-Canada, The Hebrew University-Hadassah medical School, 
      Jerusalem, Israel.
FAU - Gilburd, Boris
AU  - Gilburd B
AD  - Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of 
      Medicine, Tel Aviv University, Israel.
FAU - Schneiderman, Jacob
AU  - Schneiderman J
AUID- ORCID: 0000-0001-8651-5555
AD  - Department of Vascular Surgery, Sheba Medical Center, Sackler Faculty of 
      Medicine, Tel Aviv University, Isreal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181012
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Leptin)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, mouse)
RN  - 0 (Stat3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Echocardiography
MH  - Leptin/antagonists & inhibitors/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Myocardial Infarction/complications/genetics/*metabolism
MH  - Myocardial Reperfusion Injury/complications/genetics/*metabolism
MH  - Myocardium/*metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Smad2 Protein/metabolism
MH  - Ventricular Dysfunction, Left/blood/*etiology
MH  - Ventricular Remodeling
PMC - PMC6193573
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/10/13 06:00
MHDA- 2019/03/12 06:00
PMCR- 2018/10/12
CRDT- 2018/10/13 06:00
PHST- 2018/06/28 00:00 [received]
PHST- 2018/08/29 00:00 [accepted]
PHST- 2018/10/13 06:00 [entrez]
PHST- 2018/10/13 06:00 [pubmed]
PHST- 2019/03/12 06:00 [medline]
PHST- 2018/10/12 00:00 [pmc-release]
AID - PONE-D-18-19139 [pii]
AID - 10.1371/journal.pone.0203902 [doi]
PST - epublish
SO  - PLoS One. 2018 Oct 12;13(10):e0203902. doi: 10.1371/journal.pone.0203902. 
      eCollection 2018.