PMID- 19625611
OWN - NLM
STAT- MEDLINE
DCOM- 20091229
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 297
IP  - 6
DP  - 2009 Dec
TI  - Adverse effects of high glucose and free fatty acid on cardiomyocytes are 
      mediated by connective tissue growth factor.
PG  - C1490-500
LID - 10.1152/ajpcell.00049.2009 [doi]
AB  - Diabetic cardiomyopathy is characterized by interstitial fibrosis and 
      cardiomyocyte hypertrophy and apoptosis. Also known as CCN2, connective tissue 
      growth factor (CTGF) is implicated in the fibrosis; however, whether it 
      contributes to cardiomyocytes changes and adverse effects of high glucose and 
      lipids on these cells remains unknown. Hearts from streptozotocin-induced 
      diabetic rats had elevated CTGF and changes of pathological myocardial 
      hypertrophy, fibrosis, and cardiomyocyte apoptosis. Rat H9c2 cardiomyocytes were 
      then treated with recombinant human (rh)CTGF, high glucose, or the saturated free 
      fatty acid palmitate. Each reagent induced cell hypertrophy, as indicated by the 
      ratio of total protein to cell number, cell size, and gene expression of cardiac 
      hypertrophy marker genes atrial natriuretic peptide (ANP), and alpha-skeletal 
      actin. Each treatment also caused apoptosis measured by increased caspase3/7 
      activity, apoptotic cells by transferase-mediated dUTP nick end labeling (TUNEL) 
      assay, and lower viable cell number. Further studies showed CTGF mRNA was rapidly 
      induced by high glucose and palmitate in H9c2 cells and in mouse neonatal 
      cardiomyocyte primary cultures. small interfering RNA against CTGF blocked the 
      high glucose and palmitate induction of hypertrophy and apoptosis. In addition, 
      these CTGF effects were through the tyrosine kinase A (TrkA) receptor with 
      tyrosine kinase activity, which has previously been implicated in CTGF signaling: 
      TrkA was phosphorylated by CTGF, and a specific TrkA blocker abrogated 
      CTGF-induced effects on hypertrophy and apoptosis. For the first time in any 
      system, fatty acid is newly identified as a regulator of CTGF, and this work 
      implicates autocrine CTGF as a mediator of adverse effects of high glucose and 
      fatty acids in cardiomyocytes.
FAU - Wang, Xiaoyu
AU  - Wang X
AD  - The University of Sydney, Australia.
FAU - McLennan, Susan V
AU  - McLennan SV
FAU - Allen, Terri J
AU  - Allen TJ
FAU - Tsoutsman, Tatiana
AU  - Tsoutsman T
FAU - Semsarian, Christopher
AU  - Semsarian C
FAU - Twigg, Stephen M
AU  - Twigg SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090722
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Palmitates)
RN  - 0 (Recombinant Proteins)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis
MH  - Cardiomegaly/etiology
MH  - Cell Size/drug effects
MH  - Cells, Cultured
MH  - Connective Tissue Growth Factor/*metabolism/pharmacology
MH  - Diabetes Mellitus, 
      Experimental/complications/*metabolism/*pathology/physiopathology
MH  - Dose-Response Relationship, Drug
MH  - Glucose/*administration & dosage
MH  - Humans
MH  - Hypertrophy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/pathology
MH  - Myocytes, Cardiac/drug effects/*metabolism/*pathology
MH  - Palmitates/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkA/metabolism
MH  - Recombinant Proteins/pharmacology
EDAT- 2009/07/25 09:00
MHDA- 2009/12/30 06:00
CRDT- 2009/07/24 09:00
PHST- 2009/07/24 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2009/12/30 06:00 [medline]
AID - 00049.2009 [pii]
AID - 10.1152/ajpcell.00049.2009 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Dec;297(6):C1490-500. doi: 
      10.1152/ajpcell.00049.2009. Epub 2009 Jul 22.