Extra-adrenal mineralocorticoids and cardiovascular tissue

Simon H. Slight, Jacob Joseph, Venkataseshu K. Ganjam, Karl Weber

Research output: Contribution to journalReview article

77 Citations (Scopus)

Abstract

In experimental models where chronic inappropriate (relative to sodium intake and intravascular volume) elevations in circulating mineralocorticoids (aldosterone or deoxycorticosterone) are created, a reactive fibrosis with vascular remodeling is observed in systemic organs and the heart. Until recently, it was assumed that aldostrone was derived solely from adrenal glands via the circulation; however, there is now convincing evidence that cells of the heart and vasculature express genes responsible for the formation of both aldosterone and corticosterone and are capable of producing these steroids. Vascular endothelial and smooth muscle cells express CYP11B1 and CYP11B2, genes responsible for 11β-hydroxylase and aldosterone synthase, respectively. Furthermore, smooth muscle cells elaborate aldosterone. There is evidence that similar regulatory mechanisms operate in vascular cells as in adrenal cortex, since aldosterone synthase and 11β-hydroxylase expression are differentially modulated by low sodium/high potassium, angiotensin II and ACTH. It is likely that such localized corticosteroid production also occurs at sites of tissue repair, where populations of collagen-producing myofibroblasts, nourished by a neovasculature, predominate. Using a subcutaneous pouch model of granulation tissue we have obtained compelling data which would support such a notion. The mineralocorticoid receptor antagonist, spironolactone, severely attenuates pouch formation over a 2-week period and significantly reduces pouch wall hydroxyproline concentration. This effect is apparent even following adrenalectomy, when circulating corticosteroids are undetectable; however, with adrenalectomy alone, pouch formation is barely affected. This we took to be a possible indication of an effect of local, non-adrenal steroids in maintaining pouch tissue. Spironolactone inhibits angiogenesis. A recent clinical study demonstrates the efficacy of low-dose spironolactone in enhancing survival in patients with advanced chronic cardiac failure. Although it is not known how spironolactone brings about such an improvement in survival, we would propose that inhibition of fibrous tissue formation and/or angiogenesis might be important contributor factors. Further studies are required to address the relative contributions of circulating vs local aldosterone in promoting normal vs pathologic connective tissue formation.

Original languageEnglish (US)
Pages (from-to)1175-1184
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number6
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Mineralocorticoids
Spironolactone
Cytochrome P-450 CYP11B2
Aldosterone
Adrenalectomy
Mixed Function Oxygenases
Smooth Muscle Myocytes
Adrenal Cortex Hormones
Steroid 11-beta-Hydroxylase
Sodium
Steroids
Mineralocorticoid Receptor Antagonists
Desoxycorticosterone
Myofibroblasts
Survival
Granulation Tissue
Adrenal Cortex
Hydroxyproline
Adrenal Glands
Corticosterone

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Extra-adrenal mineralocorticoids and cardiovascular tissue. / Slight, Simon H.; Joseph, Jacob; Ganjam, Venkataseshu K.; Weber, Karl.

In: Journal of Molecular and Cellular Cardiology, Vol. 31, No. 6, 01.01.1999, p. 1175-1184.

Research output: Contribution to journalReview article

Slight, Simon H. ; Joseph, Jacob ; Ganjam, Venkataseshu K. ; Weber, Karl. / Extra-adrenal mineralocorticoids and cardiovascular tissue. In: Journal of Molecular and Cellular Cardiology. 1999 ; Vol. 31, No. 6. pp. 1175-1184.
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