Serum Concentrations of Vascular Endothelial Growth Factor, Stromal Cell-Derived Factor, Nitric Oxide and Endothelial DNA Proliferation in Development of Microvascular Pathology in Acute African Swine Fever

Abstract

There is significant evidence that pathology of the microcirculation occurs in African swine fever (ASF); however, the mechanisms by which it develops are largely unknown. In the present experimental infection study, we show that an increase in vascular permeability in the initial stages of acute ASF is dependent on viraemia and elevation of the concentration of serum nitric oxide (NO). Macrophages activated by ASF virus (ASFV) are stimulated to produce NO and simultaneously to sensitize the endothelial cells through the action of vascular endothelial growth factor Β (VEGFΒ), which is followed by an increase in VEGF-mediated endothelial permeability. In the later stages of disease, the endothelial cells undergo DNA proliferation, which may additionally provoke capillary leakage, point haemorrhages and migration of blood cells into tissues. The possible mechanism of a shift in the cell cycle from the G1 to S and G2 stages could be a direct effect of ASFV. The terminal stages of disease are characterized by triggering of compensatory mechanisms such as stimulation of the synthesis of stromal cell-derived factor-1.