Local Myocardial Overexpression of Growth Hormone Attenuates Postinfarction Remodeling and Preserves Cardiac Function

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Abstract

Background

Ventricular remodeling with chamber dilation and wall thinning is seen in postinfarction heart failure. Growth hormone induces myocardial hypertrophy when oversecreted. We hypothesized that localized myocardial hypertrophy induced by gene transfer of growth hormone could inhibit remodeling and preserve cardiac function after myocardial infarction.

Methods

Rats underwent direct intramyocardial injection of adenovirus encoding either human growth hormone (n = 9) or empty null vector as control (n = 9) 3 weeks after ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after delivery: hemodynamics, ventricular geometry, cardiomyocyte fiber size, and serum growth hormone levels.

Results

The growth hormone group had significantly better systolic cardiac function as measured by maximum left ventricular pressure (73.6 ± 6.9 mm Hg versus control 63.7 ± 7.8 mm Hg, p < 0.05) and maximum dP/dt (2845 ± 453 mm Hg/s versus 1949 ± 605 mm Hg/s, p < 0.005), and diastolic function as measured by minimum dP/dt (−2,520 ± 402 mm Hg/s versus −1,500 ± 774 mm Hg/s, p < 0.01). Ventricular geometry was preserved in the growth hormone group (ventricular diameter 12.2 ± 0.7 mm versus control 13.1 ± 0.4 mm, p < 0.05; borderzone wall thickness 2.0 ± 0.2 mm versus 1.5 ± 0.1 mm, p < 0.001), and was associated with cardiomyocyte hypertrophy (6.09 ± 0.63 μm versus 4.66 ± 0.55 μm, p < 0.005). Local myocardial expression of growth hormone was confirmed, whereas serum levels were undetectable after 3 weeks.

Conclusions

Local myocardial overexpression of growth hormone after myocardial infarction resulted in cardiomyocyte hypertrophy, attenuated ventricular remodeling, and improved systolic and diastolic cardiac function. The induction of localized myocardial hypertrophy presents a novel therapeutic approach for the treatment of ischemic heart failure.

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