The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP), purified from bone marrow and constitutively synthesized in vivo, belongs to the family of negative regulators of hematopoiesis. It protects the stem cell compartment from the toxicity of anticancer drugs and irradiation and consequently contributes to a reduction in marrow failure. This current work provides experimental evidence for another novel biologic function of AcSDKP. We report that AcSDKP is a mediator of angiogenesis, as measured by its ability to modulate endothelial cell function in vitro and angiogenesis in vivo. AcSDKP at nanomolar concentrations stimulates in vitro endothelial cell migration and differentiation into capillary-like structures on Matrigel as well as enhances the secretion of an active form of matrix metalloproteinase-1 (MMP-1). In vivo, AcSDKP promotes a significant angiogenic response in the chicken embryo chorioallantoic membrane (CAM) and in the abdominal muscle of the rat. Moreover, it induces the formation of blood vessels in Matrigel plugs implanted subcutaneously in the rat. This is the first report demonstrating the ability of AcSDKP to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo.

Background Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis Dogs with B. canis‐induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals Twenty‐nine client‐owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods Observational cross‐sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA‐1 (radioimmunoassay) and SAA was determined. Results Dogs with B. canis infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1‐716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0‐4.2 μg/mL) (P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89‐7.64 mmol/L versus 6.15 mmol/L, 4.2‐7.4 mmol/L) (P = .02), phospholipid (4.64 mmol/L, 2.6‐6.6 mmol/L versus 5.72 mmol/L, 4.68‐7.0 mmol/L) (P = .02), and α‐lipoproteins (77.5%, 27.7%‐93.5% versus 89.2%, 75.1%‐93.5%) (P = .04), and higher ApoA‐1 (1.36 U, 0.8‐2.56 U versus 0.95 U, 0.73‐1.54 U) concentrations (P = .02). Serum amyloid A correlated with high‐density lipoproteins (HDLs) diameter (rho = .43; P = .03) and ApoA‐1 (rho = .63, P < .001). Conclusions and Clinical Importance Major changes associated with B. canis‐induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA‐1 and SAA concentration increase is a unique still unexplained pathophysiological finding.