Figure 7. AngII upregulates expression levels of ICAM-1 in the vascular endothelium.

In vivo. ICAM-1 expression in microvessels (V) of the mesentery was studied by immunohistochemistry in all experimental groups of rats. Representative photomicrographs (A, B and C) illustrate the effect of calpain inhibition on AngII-induced ICAM-1 expression in rat ileal venules (V). Brown immunoperoxidase reaction product (black arrows) indicates positive staining. Percentage of venules staining positive for ICAM-1 in all experimental groups of rats are illustrated in the bar graph to the left. Control microvessels had a very low level of ICAM-1 expression (Panel A and bar graph). ICAM-1 expression levels were markedly increased in AngII infused rats (Panel B, black arrows and bar graph). Losartan, ZLLal, and PDTC treatment returned ICAM-1 expression to control levels (Panel C and bar graph). In vitro. Right bar graph shows summary of ICAM-1 expression levels in mesenteric microvascular endothelial cells (MMEC) measured by flow cytometry. Upregulation of ICAM-1 in MMEC by AngII also occurs via activation of the AT1r and it is mediated by calpain activity as demonstrated by reduced ICAM-1 expression levels in MMEC treated with losartan, ZLLal, and PDTC respectively. Loss of AngII-induced upregulation of ICAM-1 following depletion of μ-calpain with siRNA confirms the role of the μ-calpain isoform in the process of ICAM-1 upregulation by AngII. MFC indicates mean fluorescence channels values for ICAM-1 staining measured by flow cytometry. Bars represent mean ± SEM, and numbers at the base of the bars represent either the number of rats studied in each group (left graph) or the number of independent experiments (right graph). Twenty tissue sections were studied in each rat to evaluate percentage of positive venules. Black line in Panel C represents a scale of 10 μm.