Myocardial fibrosis and the concepts of cardioprotection and cardioreparation

Karl Weber, Christian G. Brilla, Scott E. Campbell, Hanumanth K. Reddy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: To examine the inter-relationship between effector hormones of the renin–angiotensin–aldosterone system and fibrosis, a determinant of abnormal myocardial stiffness, and to determine whether pharmacological interference with these hormones can prevent or regress this pathological structural remodeling. Effects of angiotensin II and aldosterone Two morphological expressions of myocardial fibrosis are evident, a perivascular and interstitial fibrosis, not related to cardiac myocyte necrosis, and microscopic scarring that replaces lost myocytes. The former, a reactive fibrosis, is related to elevations in circulating mineralocorticoids (aldosterone or deoxycorticosterone) with increased dietary sodium, and not to arterial hypertension or ventricular loading. Scarring follows the cytotoxicity associated with elevated plasma angiotensin II levels and the increased K+ excretion that accompanies chronic mineralocorticoid excess. Effects of pharmacological interference: Given the association of these hormones with fibrosis, the concept of cardioprotection was evaluated in various prevention trials. Reactive fibrosis was prevented in unilateral renal ischaemia by angiotensin converting enzyme (ACE) inhibition with captopril and in either primary or secondary hyperaldosteronism by antagonism of the aldosterone receptor with spironolactone. Scarring (and cell loss) was prevented in renal ischemia by captopril and by K+-sparing diuretics (spironolactone, amiloride) in primary hyperaldosteronism. In treatment trials, where reactive fibrosis was established, lisinopril promoted regression of the fibrosis and therefore was cardioprotective. Conclusions: Myocardial fibrosis is related to chronic mineralocorticoid excess (with increased dietary sodium), angiotensin II and increased K+ excretion. Cardioprotective and cardioreparative strategies that respectively prevent or regress the development of fibrous tissue have been demonstrated in experimental models and now merit clinical evaluation.

Original languageEnglish (US)
Pages (from-to)S87-S94
JournalJournal of Hypertension
Volume10
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Fibrosis
Mineralocorticoids
Angiotensin II
Cicatrix
Dietary Sodium
Spironolactone
Hyperaldosteronism
Captopril
Hormones
Aldosterone
Ischemia
Pharmacology
Lisinopril
Kidney
Mineralocorticoid Receptors
Desoxycorticosterone
Amiloride
Peptidyl-Dipeptidase A
Diuretics
Cardiac Myocytes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Weber, K., Brilla, C. G., Campbell, S. E., & Reddy, H. K. (1992). Myocardial fibrosis and the concepts of cardioprotection and cardioreparation. Journal of Hypertension, 10, S87-S94.

Myocardial fibrosis and the concepts of cardioprotection and cardioreparation. / Weber, Karl; Brilla, Christian G.; Campbell, Scott E.; Reddy, Hanumanth K.

In: Journal of Hypertension, Vol. 10, 01.01.1992, p. S87-S94.

Research output: Contribution to journalArticle

Weber, K, Brilla, CG, Campbell, SE & Reddy, HK 1992, 'Myocardial fibrosis and the concepts of cardioprotection and cardioreparation', Journal of Hypertension, vol. 10, pp. S87-S94.
Weber, Karl ; Brilla, Christian G. ; Campbell, Scott E. ; Reddy, Hanumanth K. / Myocardial fibrosis and the concepts of cardioprotection and cardioreparation. In: Journal of Hypertension. 1992 ; Vol. 10. pp. S87-S94.
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