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Extra-adrenal mineralocorticoids and cardiovascular tissue
S H Slight1, J Joseph, V K Ganjam
1Department of Veterinary Biomedical Sciences, University of Missouri-Columbia, Columbia, MO 65211, USA.
Journal of Molecular and Cellular Cardiology
|June 18, 1999
Summary
Local production of aldosterone in tissues, not just adrenal glands, contributes to fibrosis and vascular remodeling. Spironolactone treatment reduced tissue fibrosis and angiogenesis in experimental models, suggesting a role for local steroids in tissue repair.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Tissue Repair Mechanisms
Background:
- Chronic mineralocorticoid excess causes fibrosis and vascular remodeling in organs and the heart.
- Aldosterone was traditionally thought to be solely adrenal-derived, but local production in heart and vasculature is now recognized.
- Vascular cells express key genes (CYP11B1, CYP11B2) for steroidogenesis, similar to adrenal regulation.
Purpose of the Study:
- To investigate the role of local, non-adrenal corticosteroid production in tissue repair.
- To determine the effect of a mineralocorticoid receptor antagonist on granulation tissue formation and fibrosis.
Main Methods:
- Utilized a subcutaneous pouch model of granulation tissue in experimental animals.
- Administered spironolactone, a mineralocorticoid receptor antagonist, before and after adrenalectomy.
- Measured pouch formation, hydroxyproline concentration (a marker of collagen), and angiogenesis.
Main Results:
- Spironolactone significantly attenuated pouch formation and reduced hydroxyproline concentration, even after adrenalectomy.
- Adrenalectomy alone had minimal impact on pouch formation, suggesting a role for local steroids.
- Spironolactone demonstrated inhibitory effects on angiogenesis.
Conclusions:
- Local corticosteroid production, independent of adrenal glands, plays a significant role in granulation tissue formation and fibrosis.
- Inhibition of local mineralocorticoid signaling and/or angiogenesis by spironolactone may contribute to its therapeutic effects in conditions like heart failure.