Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing.
We have previously shown that non-myocytes present in healed 8-week infarct scar overexpress transduction proteins required for initiating the elevated deposition of structural matrix proteins in this tissue. Other work suggests that TGF-beta 1 may be involved in cardiac fibrosis and myocyte hypertrophy. However, the significance of the altered TGF-beta signaling in heart failure in the chronic phase of post-myocardial infarction (MI), particularly in the ongoing remodeling of the infarct scar, remains unexplored. Patterns of cardiac TGF beta 1 and Smad 2, 3, and 4 protein expression were investigated 8 weeks after MI and were compared to relative collagen deposition in border tissues (containing remnent myocytes) and the infarct scar (non-myocytes). Both TGF-beta 1 mRNA abundance and protein levels were significantly increased in the infarct scar v control values, and this trend was positively correlated to increased collagen type I expression. Cardiac Smad 2, 3, and 4 proteins were significantly increased in border and scar tissues v control values. Immunofluorescent studies indicated that Smad proteins localized proximal to the cellular nuclei present in the infarct scar. Decorin mRNA abundance was elevated in border and infarct scar, and the pattern of decorin immunostaining was markedly altered in remote remnant heart and scar v staining patterns of control sections. Expression of T beta RI (53 kDa) protein was significantly reduced in the scar, while the 75 kDa and 110 kDa isoforms of T beta RII were unchanged and significantly increased in scar, respectively. These results indicate that TGF-beta/Smad signaling may be involved in the remodeling of the infarct scar after the completion of wound healing per se, via ongoing stimulation of matrix deposition.
Hao
J
J
Laboratory of Molecular Cardiology, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Ju
H
H
Zhao
S
S
Junaid
A
A
Scammell-La Fleur
T
T
Dixon
I M
IM
D030201:Activin Receptors, Type I; D000818:Animals; D015153:Blotting, Western; D002921:Cicatrix / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D058575:Decorin; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000033:anatomy & histology; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004268:DNA-Binding Proteins; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat