Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model

The effect of alpha- and beta-thymosin peptides, namely prothymosin alpha (ProTalpha), thymosin alpha(1) (Talpha1) parathymosin alpha (ParaTalpha), thymosin beta(4) (Tbeta4), thymosin beta(10) (Tbeta10), and thymosin beta9 (Tbeta9), on the angiogenesis process was investigated using the chick chorioallantoic membrane as an in vivo angiogenesis model. The thymosin peptides tested were applied in 10 mul aliquots containing 0.01 4 nmoles of Tbeta4, Tbeta10 or Tbeta9, 0.016-6.66 nmoles of Talpha1, 4.1 pmoles-1.66 nmoles of ProTalpha, and 4.4 pmoles-1.76 nmoles of ParaTalpha. Phorbol 12-myristate 13-acetate and hydrocortisone were also used as positive and negative control, respectively. Tbeta4, ProTalpha and Talpha1 were found to enhance angiogenesis, while Tbeta10, Tbeta9 and ParaTalpha exhibited an inhibitory effect on the angiogenesis process. When mixtures of Tbeta4 and Tbeta10 containing active amounts of the two peptides at different proportions were applied, the promoting effect of Tbeta4 on angiogenesis was reversed in the presence of increasing concentrations of Tbeta10 and vice versa. The effect of Tbeta10, Tbeta9, ProTa and ParaTalpha in parallel with Tbeta4 and Talpha1, on the angiogenesis process was investigated for the first time as far as we know and the results of this Study offer more insight into the biological regulatory roles of thymosin peptides, and provide helpful information about their therapeutic potential. Whether these agents could be used either as inhibitors of angiogenesis in disease states where uncontrolled angiogenesis is involved, e.g. in carcinogenesis, or as angiogenesis promoters that could be useful in wound healing, fracture repair, peptic ulcers etc., remains to be further studied. (C) 2001 Elsevier Science B.V. All rights reserved.