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BMP-7 Inhibits p38 and JNK Pathways and Increases M2 Macrophage Differentiation to Reduce Atherosclerosis in Apolipoprotein E-/- Mice
| Title: | BMP-7 Inhibits p38 and JNK Pathways and Increases M2 Macrophage Differentiation to Reduce Atherosclerosis in Apolipoprotein E-/- Mice. |
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| Name(s): |
Shoulders, Heidi, Author Singla, Dinender, Committee Chair Cheng, Zixi, Committee Member Naser, Saleh, Committee Member University of Central Florida, Degree Grantor |
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| Type of Resource: | text | |
| Date Issued: | 2016 | |
| Publisher: | University of Central Florida | |
| Language(s): | English | |
| Abstract/Description: | We have previously shown that treating atherosclerosis with bone morphogenetic protein-7 (BMP-7) affects the presence of macrophage subtypes in vitro, however it remains unknown whether BMP-7 treatment affects development and progression of atherosclerosis in vivo at an early and mid-stage of the disease. We therefore performed a Day 5 (D5) and Day 28 (D28) study to examine BMP-7's potential to affect monocyte differentiation. Atherosclerotic plaque formation was developed using our standard method and ApoE-/- mice were sacrificed at D5 and D28 post-surgery. Treatment animals received intravenous injections of BMP-7 at 200(&)#181;g/kg of bodyweight. Hematoxylin and Eosin morphological stain shows that BMP-7 is capable of significantly reducing plaque accumulation at D28 post-surgery vs. PLCA group, p(<)0.05. At D5, plaque formation was reduced but not significant. Immunohistochemistry staining was performed to determine BMP-7's effect on monocytes (CD14), inflammatory M1 (iNOS) and anti-inflammatory M2 (CD206, Arginase-1) macrophages. Immunohistochemistry results show BMP-7 administration reduced pro-inflammatory monocytes and M1 macrophages at D5 and D28 compared to PLCA animals; however, monocytes were not statistically lower at D28. The anti-inflammatory M2 macrophage population was significantly less in PLCA animals compared to SHAM animals at D5 and D28. There was no significant difference in M2 macrophages between PLCA and PLCA + BMP7 animals at D5, however, by D28, PLCA + BMP7 animals showed a significant increase in M2 macrophages compared to PLCA animals. Western blot analysis confirms a significant increase in pro-survival kinase ERK and a significant reduction in pro-inflammatory kinases p38 and JNK in BMP-7 treated mice (D5 and D28, p(<)0.05). ELISA showed a significant reduction in pro-inflammatory cytokines IL-6, MCP-1, and TNF-? (D5 and D28, p(<)0.05) and a significant increase in anti-inflammatory cytokine IL-10 in BMP-7 treated mice (D5 and D28, p(<)0.05). In summary, our data indicate BMP-7 treatment induces monocyte to M2 macrophage differentiation, increases anti-inflammatory cytokine levels (IL-1ra and IL-10), and improves blow flow velocity (D5 and D28, p(<)0.05) compared to untreated animals. The mechanisms of monocyte to M2 macrophage differentiation appear to be mediated by the p38, JNK, and ERK pathways. This study suggests BMP-7 is capable of reducing inflammation and slowing progression of atherosclerosis at both an early and mid-stage of the disease. | |
| Identifier: | CFE0006504 (IID), ucf:51388 (fedora) | |
| Note(s): |
2016-12-01 M.S. Medicine, Molecular Biology and Micro Masters This record was generated from author submitted information. |
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| Subject(s): | Atherosclerosis -- Macrophages -- Monocyte Differentiation -- BMP-7 | |
| Persistent Link to This Record: | http://purl.flvc.org/ucf/fd/CFE0006504 | |
| Restrictions on Access: | public 2016-12-15 | |
| Host Institution: | UCF |
