Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function
Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function
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DOI：
10.1016/j.athoracsur.2003.12.043
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发表时间：
2004-06-01
影响因子：
4.6
通讯作者：
Woo, YJ
中科院分区：
文献类型：
--
作者：
Jayasankar, V;Bish, LT;Woo, YJ
背景。心室重构伴心室扩张和心室壁变薄见于梗死后心力衰竭。生长激素分泌过多可引起心肌肥大。我们推测生长激素基因转移诱导的局部心肌肥厚可能抑制心肌梗死后心肌重塑，维持心肌功能。在结扎左冠状动脉前降支3周后，大鼠直接在心肌内注射编码人类生长激素的腺病毒（n = 9）或空零载体作为对照（n = 9）。分娩后3周进行以下分析：血流动力学、心室几何形状、心肌细胞纤维大小和血清生长激素水平。生长激素组最大左室压（73.6 +/- 6.9 mm Hg，对照组63.7 +/- 7.8 mm Hg, p < 0.05）、最大dP/dt （2845 +/- 453 mm Hg/s，对照1949 +/- 605 mm Hg/s， p < 0.005）和最小dP/dt （- 2520 +/- 402 mm Hg/s，对照- 1500 +/- 774 mm Hg/s， p < 0.01）测量的心脏收缩功能明显更好。生长激素组的心室几何形状保持不变（心室直径12.2 +/- 0.7 mm与对照组13.1 +/- 0.4 mm相比，p < 0.05；交界区壁厚2.0 +/- 0.2 mm与1.5 +/- 0.1 mm相比，p < 0.001），并与心肌细胞肥大相关（6.09 +/- 0.63 mum与4.66 +/- 0.55 mum相比，p < 0.005）。结果证实心肌局部有生长激素表达，3周后血清未见生长激素水平。心肌梗死后局部心肌过度表达生长激素导致心肌细胞肥大，心室重构减轻，心脏收缩和舒张功能改善。局部心肌肥厚的诱导为缺血性心力衰竭的治疗提供了一种新的治疗方法。(C) 2004年由胸外科学会出版。
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 mum versus 4.66 +/- 0.55 mum, 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. (C) 2004 by The Society of Thoracic Surgeons.