Stancho Stanchev; Alexandar Iliev; Nikola Stamenov; Lyubomir Gaydarski; Kristina Petrova; Boycho Landzhov; Vidin Kirkov; Vesela Ivanova; Tihomir Dikov; Plamena Ermencheva & Georgi Kotov

Hypertension often leads to hypertensive nephropathy, characterized by nephrosclerosis and capillary rarefaction. Mast cells, tissue-resident immune cells, are implicated due to their perivascular location and release of bioactive substances, while vascular endothelial growth factor (VEGF) plays a complex role in renal health and angiogenesis. The aim of the present study was to analyze changes in mast cell number (MCN), VEGF expression and capillary density (CD) in two stages of hypertension-induced kidney injury and compare them to normotensive controls. Herein, we used spontaneously hypertensive rats (SHR) at 6 and 12 months of age and age-matched normotensive Wistar rats (WR). Kidney tissues were analyzed for mast cell tryptase, CD117 and VEGF using immunohistochemical expression and subsequent semiquantitative analysis for VEGF immunoreactivity and capillary density was quantified. Data were assessed statistically through the Mann-Whitney method. We reported a significantly higher MCN and lower CD in both 6- and 12-month-old SHR compared to controls. VEGF expression was highest in 6-month-old SHR and lowest in 12-month-old SHR. Our results suggest that the initial increase in MCN and elevated VEGF in early hypertension might be a compensatory angiogenic response to developing capillary rarefaction. However, in advanced stages, despite high MCN, depleted VEGF expression indicates the failure of this mechanism. Mast cells may contribute to capillary loss indirectly by promoting fibrosis and inflammation, which degrades the local microenvironment, overwhelming their potential pro-angiogenic capacity. These findings underscore the pivotal, albeit complex role of mast cells in the pathology of hypertensive nephropathy.

KEY WORDS: Mast cells; Vascular endothelial growth factor (VEGF); Kidney; Capillary rarefaction; Hypertension.

STANCHEV, S.; ILIEV, A.; STAMENOV, N.; GAYDARSKI, L; PETROVA, K.; LANDZHOV, B.; KIRKOV, V.; IVANOVA, V.; DIKOV, T.; ERMENCHEVA, P. & KOTOV, G. Mast cells and capillary rarefaction in hypertensive nephropathy - a potential ‘double- faced’ role? Int. J. Morphol., 43(6):1964-1972, 2025.