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Myocardial osteopontin expression is associated with left ventricular hypertrophy
1Department of Medicine and Pathology, Division of Endocrinology, Diabetes, and Hypertension, University of Southern California School of Medicine, Los Angeles, USA.
Circulation
|December 31, 1997
Summary
Osteopontin (OP) is newly found in cardiomyocytes, not inflammatory cells, in hypertrophied hearts. This suggests OP expression is linked to ventricular hypertrophy in rats and humans.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Remodeling
Background:
- Osteopontin (OP) is implicated in cardiac remodeling but its presence in myocardial tissue was unconfirmed.
- Previous studies identified OP in cardiac fibroblasts and macrophages, but not within cardiomyocytes in situ.
Purpose of the Study:
- To investigate osteopontin (OP) mRNA regulation in cultured rat cardiomyocytes.
- To determine the localization of OP mRNA in neonatal and adult rat hearts with and without hypertrophy.
- To examine OP expression in human myocardial samples with and without pathological changes.
Main Methods:
- Primary cardiomyocyte culture and stimulation with endothelin-1 (ET-1) and norepinephrine (NE).
- Quantitative real-time PCR for OP and atrial natriuretic peptide (ANP) mRNA.
- In situ hybridization and immunohistochemistry on rat and human cardiac tissues.
Main Results:
- Cultured cardiomyocytes expressed OP mRNA and protein; ET-1 and NE upregulated OP mRNA.
- OP mRNA was abundant in hypertrophied rat ventricles but minimal in normal adult hearts.
- Cardiomyocytes, not inflammatory cells, were the primary source of OP in hypertrophied human hearts and rats.
Conclusions:
- This study provides the first evidence of cardiomyocytes as a major source of osteopontin (OP) in vivo.
- Increased OP expression is strongly associated with ventricular hypertrophy in both rat and human hearts.