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Abstract: Since bone marrow-derived endothelial progenitor cells (EPCs) have been detected in adult peripheral blood, the mode of vasculogenesis in the adult tissue has caught attention in field of vascularization research. To confirm the role of EPCs in construction of new vascular loop, we took the biomaterial scaffold implanted into adult rat as an experimental model to observe and examine the actions of the EPCs in neovascularization of the material by immunohistochemistry and transmission electron microscopy. Additionally, by establishing a chemotactic migration model for vascular endothelial cells (ECs) and EPCs, the migrations of ECs and EPCs were explored in simulations. The results of 20,000 simulations showed that the number of the vascular loops assisted by the EPCs was 2–5 times that of the vascular sprouts being naturally joined. Based on the results of experiments and simulations, we conclude that the EPCs are able to assist the angiogenic sprouts in joining under the condition of plenty of the EPCs being mobilized, which aggregate at sites close to sprout tips, forming a cell cord and differentiating to ECs in situ, and become vessel segments between neighboring sprouts. This suggests that there is a difference between the adult and embryo in the manner of vasculogenesis and that a small number of EPCs can play an important role to make the new blood vessels achieve rapid functionalization. [Copyright &y& Elsevier]

Abstract: Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis in the mammalian eye, suggesting that loss of PEDF is implicated in the pathogenesis of proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. Since oxidative stress is thought to be involved in pericyte loss and dysfunction, one of the changes characteristic of early diabetic retinopathy, we investigated whether and how PEDF could protect cultured retinal pericyte against oxidative stress injury. High glucose (30 mM) increased intracellular reactive oxygen species (ROS) generation in pericytes, which was completely blocked by PEDF. High glucose or H2O2 was found to induce growth retardation and apoptotic cell death of pericytes. PEDF completely restored these cytopathic effects on pericytes. An increased ratio of bax to bcl-2 mRNA level with subsequent activation of caspase-3 was observed in high-glucose- or H2O2-exposed pericytes, which was also completely prevented by PEDF. PEDF significantly increased glutathione peroxidase (GPx) mRNA levels and activity in pericytes. Further, PEDF was found to completely inhibit high-glucose- or H2O2-induced increase in a mRNA ratio of angiopoietin-2 to angiopoietin-1 and up-regulation of VEGF mRNA levels in pericytes. PEDF mRNA levels themselves were down-regulated in high-glucose- or H2O2-exposed pericytes. These results demonstrate that PEDF protects against high-glucose- or H2O2-induced pericyte apoptosis and dysfunction through its anti-oxidative properties via GPx induction. Our present study suggests that substitution of PEDF proteins might be a promising therapeutic strategy for treatment of patients with early diabetic retinopathy. [Copyright &y& Elsevier]

Pulmonary artery vasoconstriction and vascular remodeling greatly contribute to a sustained elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) in patients with pulmonary arterial hypertension (PAH). The development of PAH involves a complex and heterogeneous constellation of multiple genetic, molecular, and humoral abnormalities, which interact in a complicated manner, presenting a final manifestation of vascular remodeling in which fibroblasts, smooth muscle and endothelial cells, and platelets all play a role. Vascular remodeling is characterized largely by medial hypertrophy due to enhanced vascular smooth muscle cell proliferation or attenuated apoptosis and to endothelial cell over-proliferation, which can result in lumen obliteration. In addition to other factors, cytoplasmic Ca2+ in particular seems to play a central role as it is involved in both the generation of force through its effects on the contractile machinery, and the initiation and propagation of cell proliferation via its effects on transcription factors, mitogens, and cell cycle components. This review focuses on the role played by cellular factors, circulating factors, and genetic molecular signaling factors that promote a proliferative, antiapoptotic, and vasoconstrictive physiological milieu leading to vascular remodeling. [Copyright &y& Elsevier]