Smooth Muscle Insulin-Like Growth Factor-1 Mediates Hypoxia-Induced Pulmonary Hypertension in Neonatal Mice
| Autor: | Jiwang Chen, Ramaswamy Ramchandran, J. Usha Raj, Qiwei Yang, Miranda Sun |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vascular smooth muscle medicine.medical_treatment Clinical Biochemistry Blood Pressure Receptor IGF Type 1 Pathogenesis Insulin-like growth factor Insulin-Like Growth Factor I Hypoxia Original Research Mice Knockout Imidazoles Up-Regulation medicine.anatomical_structure Organ Specificity Pyrazines medicine.symptom Pulmonary and Respiratory Medicine medicine.medical_specialty Systole Hypertension Pulmonary Myocytes Smooth Muscle Pulmonary Artery Vascular Remodeling 03 medical and health sciences Right ventricular hypertrophy Internal medicine medicine Animals RNA Messenger Molecular Biology Cell Proliferation Lung Hypertrophy Right Ventricular business.industry Growth factor Muscle Smooth Cell Biology Hypoxia (medical) medicine.disease Pulmonary hypertension Mice Inbred C57BL 030104 developmental biology Endocrinology Animals Newborn Chronic Disease business Proto-Oncogene Proteins c-akt Gene Deletion |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 55:779-791 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Insulin-like growth factor (IGF)-1 is a potent mitogen of vascular smooth muscle cells (SMCs), but its role in pulmonary vascular remodeling associated with pulmonary hypertension (PH) is not clear. In an earlier study, we implicated IGF-1 in the pathogenesis of hypoxia-induced PH in neonatal mice. In this study, we hypothesized that hypoxia-induced up-regulation of IGF-1 in vascular smooth muscle is directly responsible for pulmonary vascular remodeling and PH. We studied neonatal and adult mice with smooth muscle-specific deletion of IGF-1 and also used an inhibitor of IGF-1 receptor (IGF-1R), OSI-906, in neonatal mice. We found that, in neonatal mice, SMC-specific deletion of IGF-1 or IGF-1R inhibition with OSI-906 attenuated hypoxia-induced pulmonary vascular remodeling in small arteries, right ventricular hypertrophy, and right ventricular systolic pressure. Pulmonary arterial SMCs from IGF-1-deleted mice or after OSI-906 treatment exhibited reduced proliferative potential. However, in adult mice, smooth muscle-specific deletion of IGF-1 had no effect on hypoxia-induced PH. Our data suggest that vascular smooth muscle-derived IGF-1 plays a critical role in hypoxia-induced PH in neonatal mice but not in adult mice. We speculate that the IGF-1/IGF-1R axis is important in pathogenesis of PH in the developing lung and may be amenable to therapeutic manipulation in this age group. |
| Databáze: | OpenAIRE |
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