Effects of growth hormone on cardiac dysfunction and gene expression in genetic murine dilated cardiomyopathy
| Autor: | David G. Lowe, Kenneth R. Chien, John Ross, John J. Hunter, Ross G. Clark, Minoru Hongo, Jill Schoenfeld, Tsutomu Ryoke, Nancy D. Dalton |
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| Rok vydání: | 2001 |
| Předmět: |
Cardiac function curve
Null mice Cardiomyopathy Dilated medicine.medical_specialty Physiology Rhgh treatment Gene Expression Muscle Proteins Biology Growth hormone Ventricular Function Left Cardiac dysfunction Mice Physiology (medical) Internal medicine Gene expression medicine Animals Mice Knockout Myocardium Body Weight Hemodynamics Dilated cardiomyopathy Heart Organ Size LIM Domain Proteins medicine.disease Endocrinology Echocardiography Heart failure Growth Hormone Cardiology Disease Progression Cardiology and Cardiovascular Medicine |
| Zdroj: | Basic research in cardiology. 95(6) |
| ISSN: | 0300-8428 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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