Regional overexpression of insulin-like growth factor-I and transforming growth factor-beta1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy.
OBJECTIVE
Hypertrophic obstructive cardiomyopathy has been proposed to be the result of gene mutations of contractile proteins. However, we have previously shown significant elevation of insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) at the messenger RNA, protein, and receptor levels in patients with hypertrophic obstructive cardiomyopathy when compared with myocardium from patients without this disorder. We hypothesized that this growth factor overexpression is a regional phenomenon. To test this hypothesis, we compared levels of IGF-I and TGF-beta1 in hypertrophic and nonhypertrophic myocardium within the same group of patients with hypertrophic obstructive cardiomyopathy.


METHODS
Two biopsy specimens were obtained from each patient undergoing septal myectomy for severely symptomatic hypertrophic obstructive cardiomyopathy, from hypertrophied septum and from nonhypertrophied myocardium (8 patients in total). Clinical data were prospectively recorded. Messenger RNA levels for growth factor were quantified by means of multiplex reverse transcriptase-polymerase chain reaction, expressed as a densitometric ratio of growth factor/glyceraldehyde-3-phosphate dehydrogenase. Protein levels were quantified by means of chemiluminescent slot blot analysis. Growth factor proteins were used to generate a standard curve.


RESULTS
IGF-I messenger RNA and protein levels in hypertrophic myocardium were 2.6 and 2.9 times greater, respectively, than in nonhypertrophic myocardium of the same patients (both P <.01). TGF-beta 1 messenger RNA and protein levels in the hypertrophic myocardium were 2.5 and 2.8 times greater, respectively, than the levels in the nonhypertrophied myocardium (both P <.01). There was a significant correlation between the IGF-I protein ratio (hypertrophic/nonhypertrophic myocardium) and the inducible left ventricular outflow tract gradients measured at cardiac catheterization (r = 0.77, P =.025).


CONCLUSIONS
Myocardial overexpression of IGF-I and TGF-beta1 is a regional phenomenon in patients with hypertrophic obstructive cardiomyopathy and is likely involved in the pathogenesis of the disorder.
Li
Guangming
G
Division of Cardiovascular Surgery, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.
Borger
Michael A
MA
Williams
William G
WG
Weisel
Richard D
RD
Mickle
Donald A G
DA
Wigle
E Douglas
ED
Li
Ren-Ke
RK
D002312:Cardiomyopathy, Hypertrophic / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1