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J Thorac Cardiovasc Surg 2002;123:89-95
© 2002 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Regional overexpression of insulin-like growth factor-I and transforming growth factor-ß1 in the myocardium of patients with hypertrophic obstructive cardiomyopathy

From the Divisions of Cardiovascular Surgery and Cardiology, Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.

This research was supported by research grants from the Medical Research Council of Canada (grant No. MOP-14795 and MT-10392). R.-K.L. is a Career Investigator of the Heart and Stroke Foundation of Canada.

Received for publication Jan 31, 2001. Revisions requested March 22, 2001; revisions received June 20, 2001. Accepted for publication June 26, 2001. Address for reprints: Ren-Ke Li, MD, PhD, Toronto General Hospital, CCRW 1-815, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4 (E-mail: RenKe.Li{at}uhn.on.ca).

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-ß1 (TGF-ß1) 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-ß1 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-ß1 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-ß1 is a regional phenomenon in patients with hypertrophic obstructive cardiomyopathy and is likely involved in the pathogenesis of the disorder.

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