Citations

ABSTRACT Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif‐containing (TRIM)‐28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear. In this study, we investigated the role of TRIM28 in inflammatory responses and angiogenic activity of ECs for the first time. We showed that TRIM28 is the most abundant TRIM family member and is localized in nuclei of ECs. Small interfering RNA‐mediated knockdown of TRIM28 strikingly suppressed expression of TNF receptor (TNFR)‐1 and −2, decreased TNFα‐induced phosphorylation of IKKα/β and IκBα and degradation of IκBα and nuclear translocation of p65, and suppressed basal level and TNF‐α‐induced expression of chemokines and adhesion molecules, including VCAM‐1, IL‐6, ICAM‐1, E‐selectin, and monocyte chemoattractant protein (MCP)‐1. Unexpectedly, IL‐8 was potentiated by TRIM28 knockdown in ECs in an NF‐κB‐inducing kinase–dependent manner. Meanwhile, knockdown of TRIM28 inhibited expression of VEGF receptor 2 and suppressed VEGF‐induced proliferation and tube formation by ECs. Finally, knockdown of TRIM28 suppressed recruitment of ECs in vivo in a murine synthetic basement membrane model. In summary, we found that TRIM28 acts as a central factor in controlling endothelial inflammatory responses and angiogenic activities by retaining expression of TNFR‐1 and −2 and VEGF receptor 2 in ECs.—Wang, Y., Li, J., Huang Y., Dai, X., Liu, Y., Liu, Z., Wang, Y., Wang, N., Zhang, P. Tripartite motif–containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR1 and −2 and VEGFR2 in endothelial cells. FASEB J. 31, 2026–2036 (2017). www.fasebj.org

Purpose Long-term occlusion of coiled aneurysms frequently fails, probably because of poor intrasaccular healing and inadequate endothelialization across the aneurysm neck. The purpose of this study was to determine if attachment of autologous mesenchymal stem cells (MSCs) to platinum coils would improve the healing response in an elastase-induced aneurysm model in rabbits. Materials and methods With approval from the institutional animal care and use committee, aneurysms were created in rabbits and embolized with control platinum coils (Axium; Medtronic) (n=6) or coils seeded ex vivo with autologous adipose-tissue MSCs (n=7). Aneurysmal occlusion after embolization was evaluated at 1 month with angiography. Histological samples were analyzed by gross imaging and graded on the basis of neck and dome healing on H&E staining. Fibrosis was evaluated using a ratio of the total area presenting collagen. Endothelialization of the neck was quantitatively analyzed using CD31 immunohistochemistry. χ2 and Student's t-test were used to compare groups. Results Healing score (11.5 vs 8.0, p=0.019), fibrosis ratio (10.3 vs 0.13, p=0.006) and endothelialization (902 262 μm2 vs 31 810 μm2, p=0.041) were significantly greater in the MSC group. The MSC group showed marked cellular proliferation and thrombus organization, with a continuous membrane bridging the neck of the aneurysm. Angiographic stable or progressive occlusion rate was significantly lower in the MSC group (0.00, 95% CI 0.00 to 0.41) compared with controls (0.67, 95% CI 0.22 to 0.96) (p=0.02). Conclusions Autologous MSCs attached to platinum coils significantly improve histological healing, as they result in improved neck endothelialization and collagen matrix formation within the aneurysm sac.

Context: Fewer athletic injuries and lower anterior cruciate ligament injury incidence rates were noted in studies of neuromuscular-training (NMT) interventions that had high compliance rates. However, several groups have demonstrated that preventive NMT interventions were limited by low compliance rates. Objective: To descriptively analyze coach and athlete compliance with preventive NMT and compare the compliance between study arms as well as among school levels and sports. Design: Randomized, controlled clinical trial. Setting: Middle and high school athletic programs. Participants or Other Participants: A total of 52 teams, comprising 547 female athletes, were randomly assigned to the experimental or control group and followed for 1 athletic season. Intervention(s): The experimental group (n = 30 teams [301 athletes]: 12 basketball teams [125 athletes], 6 soccer teams [74 athletes], and 12 volleyball teams [102 athletes]) participated in an NMT program aimed at reducing traumatic knee injuries through a trunk-stabilization and hip-strengthening program. The control group (n = 22 teams [246 athletes]: 11 basketball teams [116 athletes], 5 soccer teams [68 athletes], and 6 volleyball teams [62 athletes]) performed a resistive rubber-band running program. Main Outcome Measure(s): Compliance with the assigned intervention protocols (3 times per week during the preseason [mean = 3.4 weeks] and 2 times per week in-season [mean = 11.9 weeks] of coaches [coach compliance] and athletes [athlete compliance]) was measured descriptively. Using an independent t test, we compared coach and athlete compliance between the study arms. A 2-way analysis of variance was calculated to compare differences between coach and athlete compliance by school level (middle and high schools) and sport (basketball, soccer, and volleyball). Results: The protocols were completed at a mean rate of 1.3 ± 1.1 times per week during the preseason and 1.2 ± 0.5 times per week in-season. A total of 88.4% of athletes completed 2/3 of the intervention sessions. Coach compliance was greater in the experimental group than in the control group (P = .014). Coach compliance did not differ by sport but was greater at the high school than the middle school (P = .001) level. Athlete compliance did not differ by study arm, sport, or school level. Conclusions: Athletes received instruction in about 50% of each protocol. Nearly 90% of athletes performed more than 2/3 of the assigned NMT interventions. The assigned intervention was performed more often in the experimental arm compared with the control arm. Coaches at the high school level complied with the given protocol more than middle school coaches did. Athletes complied well with the protocol, but coaches did not, especially at the middle school level.