Myocardial hypertrophy in transgenic mice overexpressing human interleukin 1alpha

Interleukin (IL)-1 has profound effects on nonimmune cells and organs, including the heart. The effects of IL-1 on transgenic hearts have not yet been described. We generated transgenic mice overexpressing the human IL-1 gene under control of the cytomegalovirus enhancer/chicken beta-actin promoter....

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Bibliographic Details
Published in:Journal of cardiac failure 2001-12, Vol.7 (4), p.355-364
Main Authors: Isoda, K, Kamezawa, Y, Tada, N, Sato, M, Ohsuzu, F
Format: Article
Language:English
Subjects:
Animals
Blotting, Northern
Cardiomegaly - blood
Cardiomegaly - genetics
Cardiomegaly - physiopathology
Disease Models, Animal
Female
Gene Expression
Heart Ventricles - anatomy & histology
Heart Ventricles - pathology
Hemodynamics - genetics
Interleukin-1 - genetics
Male
Mice
Mice, Transgenic
Models, Cardiovascular
Myocardium - cytology
Myocardium - pathology
Organ Size
Time Factors
Ventricular Function, Left - genetics
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Summary:Interleukin (IL)-1 has profound effects on nonimmune cells and organs, including the heart. The effects of IL-1 on transgenic hearts have not yet been described. We generated transgenic mice overexpressing the human IL-1 gene under control of the cytomegalovirus enhancer/chicken beta-actin promoter. Heart weight-body weight ratio increased 1.4- to 2.2-fold in transgenic mice compared with wild-type mice. Lung weight-body weight ratio also increased in transgenic mice, all of which died within 14 days of birth. Light microscopy revealed concentric hypertrophy with cardiomyocyte hypertrophy in all transgenic mice and pulmonary edema in some of them. Electron microscopy showed myofilament loss and an increased number of giant mitochondria, but no sarcomere disarray. Northern blotting showed that gene expression had been reprogrammed in the left ventricle of transgenic mice. Expression of fetal-type genes such as prepro-atrial natriuretic factor and beta-myosin heavy chain were increased, but voltage-dependent calcium channel messenger RNA expression was decreased in the left ventricle of transgenic mice compared with that of wild-type mice. IL-1 may cause structural and functional alterations in cardiac myocytes.
ISSN:1071-9164