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 studies^3–5 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.