Dynamics of the number of vessels during the healing process of excisional wounds in rats after the influence of chronic social stress

Annotation. Optimal vascularization of tissues is a key prerequisite for wound healing and proper tissue function. In this study, we investigated the dynamics of blood vessel density during the healing of excisional wounds in rats exposed to chronic social stress (CSS). The CSS model included social isolation and contact with aggressive conspecifics. Full-thickness wounds were created in male Wistar rats. Histological and morphometric analyses of vessels at the wound edge and periwound area were performed on days 1, 3, 7, 14, and 30 post-injury. The results showed that CSS significantly delayed angiogenesis by reducing vessel density throughout all phases of repair compared to controls. This was accompanied by alterations in mast cell activity - key regulators of loose connective tissue processes, particularly vascular and immune functions. In control animals, the typical progression was observed: initial vessel loss followed by intensive neovascular growth and remodeling. In contrast, the CSS group demonstrated impaired inflammatory response and a reduction in mast cell numbers; however, the increased functional activity of mast cells did not compensate for their reduced morphogenetic regulation of loose connective tissue and angiogenesis, resulting in persistently low vascularization. The findings indicate that chronic social stress negatively affects the cellular and molecular mechanisms of vascular network restoration during wound healing, leading to delayed regeneration and an increased risk of chronic wound pathology. Promising therapeutic strategies may involve correction of the hypothalamic-pituitary-adrenal axis and restoration of diminished local blood flow in the wound area.