Identification of a cytoplasmic linker protein as a potential target for neovascularization.

Songbo Xie, Bin Dong, Xiaodong Sun, Tala, Xianfei He, Jun Zhou, Min Liu, Dengwen Li

Atherosclerosis 2014 Apr

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Atherosclerosis and other cardiovascular diseases are serious threats to human health and become the leading cause of death in the world. Emerging evidence reveals that inhibition of plaque neovascularization could be an effective approach for the treatment of atherosclerosis. This study was conducted to identify cytoplasmic linker protein 170 as a potential target for cardiovascular diseases through modulation of neovascularization. Immunofluorescence microscopy revealed that cytoplasmic linker protein 170 was ubiquitously expressed in mouse kidney, liver, lung, normal non-atherosclerotic aorta, and atherosclerotic aorta and was partly localized in the vascular endothelium. siRNAs were introduced to human umbilical vein endothelial cells (HUVECs) and the effect of knockdown was confirmed by Western blotting. Vascularization study was assessed with matrigel-based capillary assembly, branching, and in vivo matrigel plug assays. The data showed that siRNA-mediated knockdown of the cytoplasmic linker protein remarkably compromised the assembly and branching of capillary-like blood vessels and neovascularization in vivo. Cell motility and polarity properties were then analyzed using scratch wound repair, boyden chamber, and immunofluorescence assays, and the results revealed that the cytoplasmic linker protein was critical for the motility abilities of HUVECs through its actions on cell polarity. Both in vitro and in vivo studies demonstrate the significance of the cytoplasmic linker protein for blood vessel formation. Mechanistic investigation reveals that its effect on neovascularization is orchestrated through its regulation of vascular endothelial cell polarity and motility. These findings provide the basis for exploring effective approaches to regulate neovascularization in cardiovascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Citation

Songbo Xie, Bin Dong, Xiaodong Sun, Tala, Xianfei He, Jun Zhou, Min Liu, Dengwen Li. Identification of a cytoplasmic linker protein as a potential target for neovascularization. Atherosclerosis. 2014 Apr;233(2):403-9