Induction of myocardial connective tissue growth factor in pacing-induced heart failure in pigs.
OBJECTIVE
Connective tissue growth factor (CTGF) is a secreted, heparin-binding, and extracellular matrix associated protein shown to stimulate many of the cellular events underlying fibrosis. Previous investigations have revealed that myocardial CTGF is substantially induced in ischaemic heart failure, particularly in the ischaemic and peri-ischaemic region. The purpose of the present study was to investigate to what extent myocardial induction of CTGF is a general response to congestive heart failure (CHF) and to what extent CTGF is a decisive effector of fibrosis.


METHODS
Experimental heart failure in pigs was induced by rapid pacing at 220-240 beats min(-1) for 3 weeks (CHF pigs; n = 12).


RESULTS
The CHF pigs exhibited significant left ventricular (LV) dilatation, reduced contractility, and increased cardiac filling pressures. Northern blot analysis demonstrated that myocardial CTGF mRNA levels in CHF pigs were fivefold higher (P < 0.05) than those in control pigs (n = 10). Similar elevations of immunoreactive CTGF (sixfold; P < 0.05) were observed in myocardial tissue samples prepared for Western blot analysis. Immunohistochemical analysis of myocardial tissue sections revealed predominant expression in interstitial and perivascular fibroblasts and endothelial cells. Myocardial procollagen alpha1(I) mRNA levels were also significantly elevated (sixfold; P < 0.05) in CHF pigs compared with controls, whereas myocardial tissue contents of collagen were not statistically different between the groups.


CONCLUSIONS
Induction of myocardial CTGF in heart failure is not just a response to ischaemia, but rather a general response to evolving heart failure. Yet, induction of myocardial CTGF was clearly not a sufficient effector of fibrosis.
Ahmed
M S
MS
MSD Cardiovascular Research Center and Institute for Surgical Research, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway.
von Lueder
T G
TG
Øie
E
E
Kjekshus
H
H
Attramadal
H
H
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D003094:Collagen / Q000032:analysis; D055513:Connective Tissue Growth Factor; D004452:Echocardiography / Q000379:methods; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D011347:Procollagen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine
D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011347:Procollagen; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D003094:Collagen