Angiotensin II–Induced Proliferation of Neonatal and Adult Rat Cardiac Fibroblasts
To the Editor:
Olson et al1 reported that stimulation of adult rat cardiac fibroblasts with angiotensin II (Ang II) resulted in a significant increase in 3H-thymidine incorporation over basal. Ang II indeed stimulated the proliferation of neonatal rat cardiac fibroblasts.2 However, discordant findings are reported on the in vitro effect of Ang II on the proliferation of cardiac fibroblasts of adult rats. Some studies3–5 could not detect any increase in proliferation, whereas others3 detected an increase in the proliferation of adult rat cardiac fibroblasts. It seems that the cell density greatly affected the proliferative response of adult fibroblasts to Ang II. This was nicely demonstrated by Simm and Diez3; confluent cultures (above 1×105 cells per cm2) of rat adult cardiac fibroblasts did not respond at all to Ang II, whereas proliferation occurred at lower density (below 2×104 cells per cm2). This increased proliferation was only seen after at least 40 hours of incubation and could be completely blocked by the addition of antiplatelet-derived growth factor-AA. The Ang II–induced cell proliferation of adult rat cardiac fibroblasts could be attributed to cell density-dependent expression of platelet-derived growth factor-AA.3 Cell-cell contact inhibition in high density cultures may account for the failure to induce response.
Source of Funding
This work was supported by an educational grant from AstraZeneca (Belgium).
Olson ER, Shamhart PE, Naugle JE, Meszaros JG. Angiotensin II-induced extracellular signal-regulated kinase ½ activation is mediated by protein kinase Cδ and intracellular calcium in adult rat cardiac fibroblasts. Hypertension. 2008; 51: 704–711.
Bouzeghrane F, Thibault G. Is angiotensin II a proliferative factor of cardiac fibroblasts? Cardiovasc Res. 2002; 53: 304–312.