Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin

Abstract

P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and platelets. P-selectin mediates the tethering and rolling of leukocytes along the endothelium, an early step of leukocyte extravasation. Although inflammation is a requisite process for ischemia-induced angiogenesis, little is known regarding the role of P-selectin in angiogenesis in the setting of tissue ischemia. We examined whether ischemia-induced angiogenesis is altered in P-selectin knockout (P-selectin(-/-)) mice. Angiogenesis was evaluated in a surgically induced hind-limb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD). After left hind-limb ischemia, the ischemic/normal limb LDBF ratio was persistently lower in P-selectin(-/-) mice compared with wild-type (WT) mice. CD was also significantly lower in P-selectin(-/-) mice than in WT mice on Postoperative Day 14. Fewer numbers of total CD45+ inflammatory leukocytes infiltrated into the ischemic tissues in P-selectin(-/-) mice than in WT mice, and immunohistochemical analysis revealed the number of infiltrated leukocytes expressing vascular endothelial growth factor was also decreased in P-selectin(-/-) mice. P-selectin mRNA expression was augmented after hind-limb ischemia in WT mice. In conclusion, P-selectin may play an important role in ischemia-induced angiogenesis by promoting early inflammatory mononuclear cell infiltration. P-selectin would become one possible target molecule for modulating inflammatory angiogenesis.

Regulation of vascular leak and recovery from ischemic injury by general and VE-cadherin–restricted miRNA antagonists of miR-27

“…Of interest is the fact that in the nonischemic limb, CD5-2, although it did not promote an increase in the number of capillaries (supplemental Figure 10C), it did appear to increase the level of VE-cadherin in the capillaries (supplemental Figure 10D), although this did not reach statistical significance in the 5 mice analyzed. Because ischemic recovery is influenced by both the limitation of edema and the extent of angiogenesis, 32 our results suggest that the Blockmir influences both of these aspects. The degree of recovery with CD5-2 is similar to that seen with other anti-miRNAs in this ischemic model, for example with anti-miR-100, which targets mTOR to promote angiogenesis.…”

Multi-cell Agent-based Simulation of the Microvasculature to Study the Dynamics of Circulating Inflammatory Cell Trafficking

“…Monocytes and other leukocytes are critical players in these diseases, where they have been shown to contribute to angiogenesis and microvascular remodeling, 8,21,64 atherosclerotic lesion progression and propensity to rupture, 6,7,58 as well as capillary plugging and tissue edema. 32,43,99 In cases of rampant inflammation, the participation of inflammatory cells can have an overall deleterious impact on the tissue.…”

Does regular consumption of green tea influence expression of vascular endothelial growth factor and its receptor in aged rat erectile tissue? Possible implications for vasculogenic erectile dysfunction progression

“…On the other hand, vasculogenic ED associated with corpora cavernosa atherosclerosis could be considered a hypoxia/ischemia pathology per se, thus acting as an angiogenesis inducer (Egami et al 2006).…”