Angiotensin Receptor Stimulation of Transforming Growth Factor-β in Rat Skin and Wound Healing

Abstract

Numerous studies have implicated the octapeptide angiotensin II (ANG II) as a growth factor. There is a link between angiotensin and cell growth in cardiovascular hypertrophy, in proto-oncogene regulation¹ and in the excessive smooth muscle cell proliferation that occurs after balloon catheter injury.² The neointimal regrowth has been shown to be decreased by treatment with angiotensin-converting enzyme (ACE) inhibitors and losartan, an AT₁ receptor antagonist.³ Although ACE inhibitors have many actions, further work by Powell et al. ⁴ support the role of ANG II as the growth promotor of vascular smooth muscle cells and matrix protein synthesis. Further evidence is that in aortic smooth muscle cells in culture, ANG II stimulates [³H]thymidine incorporation but the effect depends on the types of cell cultures used and the presence of serum or platelet-derived growth factor or epidermal growth factor.⁵ Thus the growth action of ANG II may depend on its ability to stimulate other growth factors. Majesky et al. ⁶ showed that transforming growth factor-β (TGF-β) mRNA expression in the blood vessel wall was increased after vascular injury. The neointimal smooth muscle cells had positive staining for TGF-β, and taken together these studies suggest that angiotensin in the vascular wall stimulates paracrine production of TGF-β and other growth factors.