title: Identification of a cytoplasmic linker protein as a potential target for neovascularization.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Songbo
authors: S
authors: Xie
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Bin
authors: B
authors: Dong
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Xiaodong
authors: X
authors: Sun
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Tala
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Xianfei
authors: X
authors: He
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
authors: Jun
authors: J
authors: Zhou
authors: Department of Biochemistry, Basic Medical College, Tianjin Medical University, Tianjin 300070, China. Electronic address: minliu@tijmu.edu.cn.
authors: Min
authors: M
authors: Liu
authors: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: dwli@nankai.edu.cn.
authors: Dengwen
authors: D
authors: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D002196:Capillaries / Q000254:growth & development; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D003094:Collagen; D004041:Dietary Fats / Q000633:toxicity; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000517:prevention & control*; D009928:Organ Specificity; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000503:physiopathology; D011509:Proteoglycans; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; D004338:Drug Combinations; D007797:Laminin; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; C076744:cytoplasmic linker protein 170; D003094:Collagen
keywords: Atherosclerosis; Cardiovascular disease; Cytoplasmic linker protein; Motility; Neovascularization; Polarity