Activin receptor-like kinase 1 and its roles in angiogenesis / 中国病理生理杂志

Activin receptor-like kinase (ALK) 1 is a transforming growth factor-β/bone morphogenetic pro-teins superfamily type Ⅰ receptor, predominantly expressed in active endothelial cells. ALK1 has been shown to play a piv-otal role in regulating angiogenesis, which is involved in vascular formation during embryonic and early postnatal develop-ment and angiogenesis-related diseases, such as cardiovascular disorders and tumor. Understanding the exact function of ALK1 in angiogenesis will provide theoretical basis for anti-angiogenic strategy of ALK1 inhibition. In the present study, we briefly recapitulate ALK1 signaling pathway and its role in blood vessel formation and pathological neovascularization.

Role of Hedgehog signaling pathway in the development of retinal cells and pathological angiogenesis / 中华实验眼科杂志

The pathological growth of retinal cells and ocular pathologic angiogenesis can be seen in a variety of eye diseases,which seriously affect the visual acuity of patients.The Hedgehog signal pathway has been demonstrated to be involved in the development of retinal ganglion cells,amacrine cells,cone cells and rod cells,Müller glial cells and retinal pigment epithelial cells.This paper discusses the function of Hedgehog signal pathway in the development of retinal cells and ocular pathologic angiogenesis,which may provide a new therapeutic target for retinal and ocular vascular diseases.

Expression of Nestin on Endothelial Cells and Pericytes During Retinal Vascular Development in Mouse

PURPOSE: Nestin, a marker of neural stem cells, is expressed in Müller cells during retinal development. However, the role of nestin in retinal vascular development is not well established. Thus, we investigated the expression of nestin in developmental mouse retina and identified which retinal cells are related to the expression of nestin during the retinal vascular development. METHODS: Eyes were enucleated from C57BL/6 mice on postnatal day (P) 4, P8, P12, P16 and P26. Immunofluorescence was used to evaluate nestin expression in relation to endothelial cells (isolectin B4), pericytes (neural/glial antigen 2) and astrocytes (glial fibrillary acidic protein). RESULTS: Nestin was strongly expressed from the ganglion cell layer to retinoblast layer at P4. At P8, P12 and P16, the expression of nestin was observed from the upper border of the ganglion cell layer, and vertically penetrating to outer nuclear layer. At P26, the expression of nestin was decreased and confined to the ganglion cell layer and inner nuclear layer. Interestingly, there was strong vascular shape expression of nestin at all stages. The superficial, deep and intermediate vascular plexus was completely merged with nestin expression at P4, P8, P12 and P16. In addition, the nestin expression merged with pericytes but not with astrocytes. CONCLUSIONS: Nestin was expressed in endothelial cells and pericytes during retinal vascular development in the retina. These results suggest that nestin could play an important role in developmental angiogenesis via interplay with endothelial cells and pericytes.

Pulmonary vascular development,diagnosis and treatment for pulmonary hypertension in preterm in-fants with bronchopulmonary dysplasia / 中国小儿急救医学

It is well known that pulmonary hypertension(PH) is one severe complication of bron-chopulmonary dysplasia( BPD) that is associated with high mortality. Aberrant pulmonary vascular growth, abnormal vasoreactivity and pulmonary vascular remodeling may ultimately lead to PH. Symptoms of PH of-ten overlap those of BPD itself. Furthermore,the emergence of symptoms may indicate that the disease has already progressed to a late, less reversible phase, thereby supporting arguments for screening all infants at risk. Echocardiography is non-invasive and widely available,and is currently the most commonly used screen-ing modality for PH in infants with BPD. Because the incidence of associated cardiovascular anomalies is high,cardiac catheterization and CT scanning of the chest should be considered in all infants who have signifi-cant PH despite optimal management of their lung disease. Early diagnosis and aggressive specific drug thera-py can improve the outcome for these patients.

Effect of Pakl on embryonic vascular development and the related mechanisms / 第二军医大学学报

Objective To investigate the effects of p21-activated kinase 1 (Pakl) on embryonic vascular development and to discuss the underlying mechanisms. Methods In vitro transcription reactions were performed with the linearized PCS2-caPakl templates and SP6 RNA polymerase. Overexpression of constitutively active Pakl (caPakl) mRNA in one-cell stage embryos of zebrafish was achieved by microinjection. The morphological changes of the embryos were observed under an inverted microscope and the ultrastructure of vessel was confirmed by transmission electron microscope. PCS2-caPak1 was used to transfect into human umbilical vein endothelial cells (HUVECs) via LipofectamineLTX; cell viability was tested by MTT based assay; and apoptosis of HUVECs was analyzed by flow cytometry with Annexin V /7-AAD double-staining. Results Obvious cerebral hemorrhage was observed in the embryo of zebrafish at 30-36 h after fertilization, and the hemorrhage phenotype was observed in the caPakl overexpression group, with the incidence of hemorrhage being 25%-30%. In the caPakl overexpression group, transmission electron microscope found damaged vascular endothelial cells in the bleeding sites. Inverted microscope also showed abnormal morphology of cultured cells with caPakl overexpression, rounded up and started to detach from the dishes. MTT assay showed significantly decreased cell survival in the caPakl overexpression group (P<0. 0l), and flow cytometry demonstrated a significantly higher rate of cell apoptosis (P<0. 0l). Conclusion Pakl overexpression may affect embryonic vasculogenesis through inducing apoptosis of vascular endothelial cells in zebrafish.

Role of Axonal Guidance Factor Netrin-1 in Human Placental Vascular Growth / 华中科技大学学报（医学）（英德文版）

This study investigated the role of netrin-1 in placental vascular development.In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis.Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability,migration and tubular formation were studied,in order to examine the effects of netrin-1.The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro.In addition,netrin-1 enhanced the viability,migration and tube formation of HPMECs.Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.

Vascular Aspects of Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is characterized by arrest of vascular and alveolar development in premature infants. Recent advances in neonatology have increased the survival of immature babies. Consequently, the prevalence of BPD is increasing. Animal studies and autopsy findings of BPD have demonstrated interruption in vascular development and reversal of lung injury through promotion of vasculogenesis. Normal lung development is driven by temporal and spatial specific growth factors and cell- to- cell signaling in vascular development. Lung injury through various pathways causes disruption in this complex interactive process and results in aberrant vascular development and subsequent BPD. By understanding the regulation of vascular growth of the lung, it would be possible to find new targets in the treatment and prevention of BPD in premature infants.

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