Pathogenesis of hypertrophic cardiomyopathy. Impact of growth factors on left ventricular anatomy.
OBJECTIVE
The aim of this study was to evaluate the effect of insulin-like growth factor 1 (IGF1) and transforming growth factor beta-1 (TGFbeta-1) on collagen turnover, left ventricular (LV) hypertrophy and on passive diastolic function of the LV in hypertrophic cardiomyopathy (HCM).


METHODS
This study group comprised 34 patients with non-dilated HCM. Procollagen I amino-terminal propeptide (PINP) and collagen I carboxy-terminal telopeptide (ICTP) were measured by radioimmunoassay. Matrix metalloproteinase 9 (MMP 9), IGF1 and TGFalfa-1 were determined by enzyme-linked immunosorbent assay. The difference in duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves, was considered as an estimate of passive diastolic function; the ratio between the peak flow velocity at rapid filling at the mitral level (E) and E' measured by tissue Doppler was considered an estimate of active diastolic function. LV mass was measured and normalized to body surface area (LVMi) by cardiac magnetic resonance imaging.


RESULTS
LVMi correlates to E/E' (r=0.597, P=0.019 ) and is inversely related to A-Ar (r=0.453, P=0.015). TGFbeta-1 is directly related to active MMP 9 (r=0.439, P=0.012 ). IGF1 is directly related to PICP-ICTP (r=0.347, P=0.501), that expresses the balance between collagen I synthesis and its degradation.


CONCLUSIONS
The study demonstrated that in HCM, LVMi influences active and passive diastolic dysfunction and that IGF1 stimulates collagen synthesis and TGFbeta-1 is related to LV hypertrophy.
Migliore
T
T
Department of Clinical Medicine, Federico II University, Naples, Italy.
Parrella
L S
LS
Caputi
A
A
Silvestri
N
N
Romano
R
R
Pace
L
L
Imbriaco
M
M
Losi
M A
MA
Betocchi
S
S
D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis* / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I; D015150:Echocardiography, Doppler; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides; D011347:Procollagen / Q000378:metabolism; D011863:Radioimmunoassay; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000378:metabolism
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D020780:Matrix Metalloproteinase 9