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Aldosterone increases osteopontin gene expression in rat endothelial cells
Toru Sugiyama1, Takanobu Yoshimoto, Yuki Hirono
1Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
Biochemical and Biophysical Research Communications
|August 30, 2005
Summary
Aldosterone, a risk hormone for cardiovascular disease, directly increases osteopontin gene expression in rat aortic endothelial cells. This aldosterone-induced osteopontin may initiate cardiovascular inflammation and fibrosis via mineralocorticoid receptor (MR) signaling.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Biology
Background:
- Aldosterone is a key hormone implicated in cardiovascular disease progression.
- The precise cellular mechanisms underlying aldosterone's cardiovascular effects remain incompletely understood.
- Investigating aldosterone's impact on endothelial cells is crucial for understanding cardiovascular injury.
Purpose of the Study:
- To determine if aldosterone induces pro-inflammatory gene expression in rat aortic endothelial cells.
- To elucidate the cellular and molecular pathways involved in aldosterone's effects on endothelial cells.
Main Methods:
- Treatment of rat aortic endothelial cells with varying concentrations and durations of aldosterone.
- Quantitative analysis of osteopontin mRNA and protein levels.
- Assessment of adhesion molecules and chemokine expression.
- Pharmacological inhibition using mineralocorticoid receptor (MR) and glucocorticoid receptor antagonists (spironolactone, RU486).
- Inhibition of transcription (actinomycin D) and protein synthesis (cycloheximide).
Main Results:
- Aldosterone significantly upregulated osteopontin mRNA and protein expression in a time- and dose-dependent manner.
- Aldosterone did not affect the expression of adhesion molecules or chemokines.
- The effect of aldosterone was mediated by the mineralocorticoid receptor (MR), as it was blocked by spironolactone but not RU486.
- Aldosterone-induced osteopontin expression was dependent on both transcription and protein synthesis, confirmed by actinomycin D and cycloheximide treatments.
Conclusions:
- Aldosterone directly stimulates osteopontin gene expression in endothelial cells through MR-mediated genomic action.
- This aldosterone-induced osteopontin expression may play a significant role in initiating inflammation and fibrosis in cardiovascular tissues.
- The findings provide novel insights into the molecular mechanisms of aldosterone-induced cardiovascular injury.