Disorders in angiogenesis and redox pathways are main factors contributing to the progression of rheumatoid arthritis: a comparative proteomics study.

OBJECTIVE: To clarify the pathogenesis of rheumatoid arthritis (RA) by comparing protein expression in fibroblast-like synoviocytes (FLS) from patients with RA with that in FLS from normal subjects, using proteomics analysis. METHODS: Proteins extracted from primary cultures of FLS obtained from 50 patients with RA and 10 normal subjects were analyzed by automated 2-dimensional nano-electrospray ionization liquid chromatography tandem mass spectometry. Differentially expressed proteins were screened by 2-sample t-test (P < 0.05) and fold change (>1.5), based on the bioinformatics analysis. The expression of vasculature development-related proteins (Thy-1, connective tissue growth factor [CTGF], and thrombospondin 1 [TSP-1]) and redox-related proteins (superoxide dismutase 2 [SOD2]) in synovial tissue was confirmed by real-time polymerase chain reaction and Western blotting. The effect of Thy-1 and CTGF knockdown on Thy-1, CTGF, TSP-1, and vascular endothelial growth factor (VEGF) was analyzed by RNA interference experiments. RESULTS: According to the criteria of having >1 unique peptide per protein present and a false discovery rate of ≤5%, 1,060 proteins were identified from patients with RA, and 1,292 proteins were identified from normal subjects, from which 100 differentially expressed proteins were screened out from the RA proteins. Of these, 46 proteins were up-regulated, and the remaining 54 proteins were down-regulated. Gene ontology and pathway analyses showed that 6 vasculature development-related proteins were up-regulated, including Thy-1, CTGF, and TSP-1, while 11 redox-related proteins were down-regulated, including SOD2. The results were consistent with those obtained using mass spectrometry. Thy-1, VEGF, CTGF, and TSP-1 were down-regulated after Thy-1 knockdown, and VEGF and CTGF were down-regulated after CTGF knockdown. Recombinant human CTGF could enhance proliferation and Transwell migration of human umbilical vein endothelial cells. CONCLUSION: Up-regulation of vasculature development-related proteins and down-regulation of redox-related proteins in FLS are predominant factors that may contribute to the pathogenesis of RA.

Three-dimensional reconstruction of the uterine vascular supply through vascular casting and thin slice computed tomography scanning.

It was the objective of this study to construct a model of the uterine vascular supply through vascular casting and thin slice computed tomography scanning. This will provide a teaching aide for the understanding of uterine artery embolization (UAE) procedures, as well as normal uterine and ovarian arterial anatomy. Using 20% chlorinated poly vinyl chloride, we infused and cast a set of a normal uterus, vagina and bilateral adnexa through the uterine artery and ovarian artery. After thin slice CT scanning, we obtained the three-dimensional (3D) reconstruction by maximum intensity projection (MIP) and surface-shaded display (SSD), and then observed its figure and characteristics. A model of the uterine vascular supply can be successfully reconstructed by vascular casting and thin slice CT scanning. The 3D reconstruction offers a clear view of the course of the uterine artery and its blood supply distribution. It has two major branches: The intramuscular uterine branch and the cervicovaginal branch (1). Blood supply is generally unilateral, with communicating branches between the two sides and possible anastomoses between the arterial blood supply of the uterus and the ovaries. The major blood supply of the cervix comes from the cervicovaginal branch of the uterine artery, while the vaginal arterial supply derives directly from the internal iliac artery. The CT technique allows real-time 360 degrees rotation and changes in model for in-depth study of the vascular network and its adjacent tissues. It is possible to construct an in vitro uterine arterial network by vascular casting and CT scanning, which can provide unique insight into the female genitourinary system arterial network. Based on this, we can create reconstructions as well as models for different diseases such as leiomyomata, adenomyosis, and endometrial cancer. These models will provide morphological evidence to the interventional therapy and UAE teaching in Obstetrics and Gynecology.