Effects of growth hormone on cardiac dysfunction and gene expression in genetic murine dilated cardiomyopathy

被引：0

作者：

M. Hongo

T. Ryoke

J. Schoenfeld

J. Hunter

N. Dalton

R. Clark

D. Lowe

K. Chien

J. Ross Jr.

机构：

[1] The First Department of Internal Medicine,

[2] Sinshu University School of Medicine,undefined

[3] 3-1-1 Asahi,undefined

[4] Matsumoto 390,undefined

[5] Japan,undefined

[6] Konan Saint Hill Hospital,undefined

[7] Department of Cardiology,undefined

[8] 108 Higashiwari,undefined

[9] Konan,undefined

[10] Ube,undefined

[11] Yamaguchi 759-0204,undefined

[12] Japan,undefined

[13] Genentech,undefined

[14] Inc.,undefined

[15] Idna Way,undefined

[16] South San Francisco,undefined

[17] CA94080-4990,undefined

[18] USA,undefined

[19] 500 Doyle Park Drive,undefined

[20] Santa Rosa,undefined

[21] CA 95405,undefined

[22] USA,undefined

[23] Division of Cardiology,undefined

[24] Department of Medicine,undefined

[25] University of California,undefined

[26] San Diego 92093-0613B,undefined

[27] USA,undefined

[28] Research Centre for Developmental Medicine & Biology,undefined

[29] University of Auckland School of Medicine,undefined

[30] Private Bag 92019,undefined

[31] Auckland,undefined

[32] NZ,undefined

来源：

Basic Research in Cardiology | 2000年 / 95卷

关键词：

Key words Heart failure – gene disruption – gene knockout – left ventricular function – muscle LIM protein;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Beneficial cardiac effects of growth hormone (GH) have been shown in heart failure in several settings, but studies are lacking on this and other forms of treatment in the cardiomyopathic (CM) mouse heart. In mice with dilated cardiomyopathy due to disruption of the muscle LIM protein (MLP) gene [MLP null mice (MLP–/–)], natural history was first assessed by an initial echocardiogram at 8 weeks and a later follow-up study (n = 31). In most mice, left ventricular (LV) dilation increased and/or function decreased by 5 months, and 3 of 12 mice followed for 9 months died. At the end of follow-up, 22 MLP–/– mice (average age 10.2 months) had both LV dilation and reduced LV function and were selected for studies of GH effects on cardiac function and gene expression; mice were randomized to vehicle (controls) or recombinant human (rh) GH and restudied after 2 weeks. In the GH-treated group compared to the control group, LV % fractional shortening and LV wall thickness (echocardiography) were increased, the LV dP/dtmax (catheter-tip micromanometry) was enhanced, and LV relaxation (tau) improved; however, the LV weight was not significantly increased. The LV expression of many genes was altered in MLP–/– mice, and several were influenced by GH. Thus, short-term RhGH treatment improved LV function in a setting of chronic cardiac deterioration and significantly reduced elevated LV mRNA expression of some (ANP, BNP) but not other members of the embryonic gene program. The MLP null cardiomyopathic mouse can be useful for exploring altered signalling and therapeutic interventions in heart failure.

引用

页码：431 / 441

页数：10