Acetyl Ser-Asp-Lys-Pro is formed in bone marrow cells by enzymatic processing of thymosin β4. It inhibits the entry of pluripotent hemopoietic stem cells into S-phase of the cell cycle and protects against Ara-C lethality in mice.

N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) is a specific substrate for the N-terminal site of ACE and increases five-fold during ACE inhibitor therapy. AcSDKP inhibited the proliferation of isolated cardiac fibroblasts (P<0.05) but significantly stimulated the proliferation of vascular smooth muscle cells. Flow cytometry of rat cardiac fibroblasts treated with AcSDKP showed significant inhibition of cell progression from G0/G1 phase to S phase. In cardiac fibroblasts transfected with a Smad-sensitive luciferase reporter construct, AcSDKP decreased luciferase activity by 55±9.7% (P=0.01). Additionally, AcSDKP decreased phosphorylation and nuclear translocation of Smad2 in cardiac fibroblasts. In conclusion, AcSDKP inhibits the growth of cardiac fibroblasts and TGFbeta1-stimulated phosphorylation of Smad2. Because AcSDKP increases substantially during ACE inhibitor therapy, this suggests a novel pathway independent of angiotensin II by which ACE inhibitors can inhibit cardiac fibrosis.