Background and aimsDetermine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm).MethodsAAA was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm.ResultsPhospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model.ConclusionsActivation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA.
Electrospun polymer nanofibers have gained much attention in blood vessel tissue engineering. However, conventional nanofiber materials with the deficiencies of slow endothelialization and thrombosis are not effective in promoting blood vessel tissue repair and regeneration. Herein, biomimetic gelatin (Gt)/polycaprolactone (PCL) composite nanofibers incorporating a different amount of chondroitin sulfate (CS) were developed via electrospinning technology to investigate their effects on antithrombogenicity and endothelial cell affinity. Varying CS concentrations in PG nanofibers affects fiber morphology and diameter. The CS/Gt/PCL nanofibers have suitable porosity (~ 80%) and PBS solution absorption (up to 650%). The introduction of CS in Gt/PCL nanofibers greatly enhances their anticoagulant properties, prolongs their coagulation time, and facilitates cell responses. Particularly, 10%CS/Gt/PCL nanofibers display favorable cell attachment, elongation, and proliferation. Thus, the Gt/PCL nanofibers containing a certain amount of CS could be excellent candidates as a promising tissue-engineering scaffold in blood vessel repair and regeneration.
This study aims to validate whether bone marrow stromal cells (BMSCs) transplantation could promote the resolution and recanalization of deep vein thrombosis (DVT) and to explore the underlying mechanism. The right hind femoral vein was embolized to establish the DVT rabbit model. BMSCs from New Zealand white rabbits were isolated and identified, and then injected into DVT rabbits. After that, the extent of angiogenesis was determined by the amount of capillaries that were positive for antibody against vWF. Macrophage infiltration was measured by immunohistochemistry with F4/80 antibody. M1 or M2 macrophages were identified as F4/80 + CD11c + or F4/80 + CD206 + cells by using flow cytometry analysis, respectively. BMSCs were successfully isolated and identified. BMSCs transplantation promotes macrophage infiltration and angiogenesis in DVT rabbits. BMSCs transplantation causes M1/M2 polarization, altered cytokine production and increased monocyte chemotactic protein 1 (MCP-1) protein expression in DVT rabbits. However, injection of MCP-1 protein not only reversed the effects of BMSCs transplantation on macrophage infiltration and angiogenesis, but also reversed the effects of BMSCs transplantation on M1/M2 polarization and cytokine production in DVT rabbits. BMSCs transplantation promotes the resolution and recanalization of DVT in rabbits through regulating macrophage infiltration and angiogenesis, the underlying mechanism is associated with MCP-1 expression.
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