Aldosterone and D-glucose stimulate the proliferation of human cardiac myofibroblasts in vitro.
The renin-angiotensin-aldosterone-system appears to be involved in the development of cardiac fibrosis in rodents, characterized by nonepithelial cell proliferation and changes in the extracellular matrix. The aim of our study was to investigate the effect of high aldosterone concentrations on the proliferation of human cardiac interstitial cells in vitro. In addition, the effect of D-glucose as another risk factor for fibrosis, eg, in the diabetic heart, was investigated. Human cardiac myofibroblast cultures were established, and growth rates were measured by WST-1 assay in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). Cells in culture showed a significant increase in number between 24 to 72 hours of cultivation under basal conditions (DMEM, 10% fetal calf serum). Aldosterone at high concentrations (10(-8) and 10(-7) mol/L) significantly (P<0.01) increased the proliferation of cultured cardiac myofibroblasts. Comparable effects were observed after incubation of the cells with high D-glucose concentrations (15 and 25 mmol/L, P<0.01). No additive growth stimulation was evident when the cells were incubated in medium containing both aldosterone and D -glucose. These results suggest a role for aldosterone and glucose in mediating the cardiac fibrosis through stimulation of myofibroblast growth in patients with dysregulated renin-angiotensin-aldosterone-system (especially hyperaldosteronism) and impaired glucose homeostasis.
Neumann
Susanne
S
Department of Internal Medicine II, University of Leipzig, Germany.
Huse
Klaus
K
Semrau
Robert
R
Diegeler
Anno
A
Gebhardt
Rolf
R
Buniatian
Gayane Hrachia
GH
Scholz
Gerhard H
GH
D000199:Actins / Q000032:analysis; D000368:Aged; D000450:Aldosterone / Q000494:pharmacology*; D018845:CD11 Antigens / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005947:Glucose / Q000494:pharmacology*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
D000199:Actins; D018845:CD11 Antigens; D018950:Lipopolysaccharide Receptors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000450:Aldosterone; D005947:Glucose