SIKVAV promotion proliferation of vascular endothelial cells and related mechanisms

Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements.

The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms.

MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 μg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot.

SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV's role in promoting vascular endothelial cell proliferation via these pathways.

The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.