Temporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone

Scott E. Campbell, Joseph S. Janicki, Karl Weber

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Chronic activation of the circulating renin-angiotensin-aldosterone system (RAAS), as can occur with unilateral renal ischemia (URI), is associated with an adverse structural remodeling of the right and left ventricles characterized by reparative (i.e., microscopic scars) and reactive (i.e., perivascular/interstitial) fibrosis. The time course and cells involved in fibroplastic and fibrogenic phases of these events are unclear. Hearts were examined over the course of 8 weeks in rats infused with either angiotensin II or aldosterone, and compared to rats with URI. Tissue sections from the same heart were stained with hematoxylin and eosin, collagen specific picrosirius red, or immunolabeled with PCNA or α smooth muscle actin antibody. With angiotensin II or renal ischemia, fibroblast proliferation, presenting as focal accumulations at both sites of myocyte necrosis and widespread perivascular locations, was present in each ventricle on days 2 and 4, but not thereafter. α-Smooth muscle actin containing cells (myofibroblasts) appeared at day 2 and persisted through week 2 with renal ischemia and week 6 with angiotensin II. Macrophages, neutrophils and lymphocytes were transiently found at sites of necrosis between day 2-4 of renal ischemia. AngII-induced necrotic sites were characterized by macrophages and lymphocytes from day 2 through week 6, and neutrophils at day 2-4. Increased collagen volume fraction, presenting as immature scars associated with fibroblast clusters and interstitial/perivascular fibrosis, was evident on day 14 in both ventricles. In contrast, fibroblast proliferation during aldosterone infusion did not appear in both ventricles until week 3 and was associated with a subsequent reparative and reactive fibrosis as early as 4 weeks. Myofibroblasts became evident between 3-6 weeks; macrophages and lymphocytes were seen between 3-8 weeks. Neutrophils were not seen at any time point with aldosterone. Thus, the temporal cellular response and appearance of myocardial fibrosis associated with chronic elevations in angiotensin II and/or aldosterone differ. We conclude that separate pathogenic mechanisms are operative with these effector hormones of the RAAS.

Original languageEnglish (US)
Pages (from-to)1545-1560
Number of pages16
JournalJournal of Molecular and Cellular Cardiology
Volume27
Issue number8
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Aldosterone
Angiotensin II
Ischemia
Fibroblasts
Phenotype
Kidney
Fibrosis
Neutrophils
Myofibroblasts
Macrophages
Lymphocytes
Renin-Angiotensin System
Cicatrix
Smooth Muscle
Actins
Necrosis
Collagen
Proliferating Cell Nuclear Antigen
Hematoxylin
Eosine Yellowish-(YS)

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Temporal differences in fibroblast proliferation and phenotype expression in response to chronic administration of angiotensin II or aldosterone. / Campbell, Scott E.; Janicki, Joseph S.; Weber, Karl.

In: Journal of Molecular and Cellular Cardiology, Vol. 27, No. 8, 01.01.1995, p. 1545-1560.

Research output: Contribution to journalArticle

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