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Bone Morphogenetic Protein-7 Attenuates Inflammation and Apoptosis and Improves Cardiac Function in Diabetes
| Title: | Bone Morphogenetic Protein-7 Attenuates Inflammation and Apoptosis and Improves Cardiac Function in Diabetes. |
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| Name(s): |
Urbina, Princess, Author Singla, Dinender, Committee Chair Naser, Saleh, Committee Member Zhao, Jihe, Committee Member , Committee Member University of Central Florida, Degree Grantor |
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| Type of Resource: | text | |
| Date Issued: | 2013 | |
| Publisher: | University of Central Florida | |
| Language(s): | English | |
| Abstract/Description: | Bone Morphogenetic Protein-7 (BMP-7) belongs to the transforming growth factor-? (TGF?) family of cytokines has is known to have potent anti-inflammatory properties. It has been used in patients to treat osteoporosis clinically and has been reported to treat diabetic nephropathy in murine models. Moreover, studies show that inflammation is up-regulated in patients with pre-diabetes (PD). We, therefore, hypothesize that the administration of BMP-7 will attenuate inflammation in the heart of Streptozotocin (STZ)-induced PD mice. In this study, we divided C57Bl/6 mice into three groups: CONTROL, PD, and PD+BMP-7. CONTROL mice received intraperitoneal (i.p.) injections of Sodium Citrate Buffer while PD and PD+BMP-7 groups received i.p. injections of Streptozotocin (STZ) for two days. In addition, PD+BMP-7 mice received intravenous injections (i.v.) of BMP-7 (200(&)#181;g/kg) on the last day of STZ injection and for the following two days. Animals were sacrificed 21 days post last injection and examined for levels of oxidative stress, inflammatory immune response, apoptosis, fibrosis and cardiac function. Our results indicate significant glucose intolerance in PD mice (p(<)0.05), which was attenuated in the PD+BMP-7 group (p(<)0.05). We also observed increased oxidative stress (p(<)0.001) and secretion of pro-inflammatory cytokines (p(<)0.05), interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?), in PD mice as compared with the controls. PD+BMP-7 mice revealed significant up-regulation of M2 macrophages (p(<)0.05) and secretion of anti-inflammatory cytokines (p(<)0.05), interleukin-10 (IL-10) and interleukin-1RA (IL-1RA), as compared to PD mice. This was observed with a concomitant down-regulation of pro-inflammatory cytokines, IL-6 and TNF-?, as compared to the PD group. Moreover, we observed significantly increased cardiac apoptosis and fibrosis in PD mice (p(<)0.001) as compared to the control group. These observations, however, were down-regulated upon treatment with BMP-7. Lastly, analysis of echocardiograms revealed significantly depressed cardiac function in PD mice as compared with controls, while the PD+BMP-7 group presented improved cardiac function compared to PD mice. In conclusion, our data suggest that treatment with BMP-7 is effective in alleviating cardiac inflammation, inhibiting apoptosis, blunting cardiac remodeling and improving cardiac function in the hearts of STZ-induced PD mice. This reveals the potential of BMP-7 as a therapy in PD patients who present an increased inflammatory immune response. | |
| Identifier: | CFE0004765 (IID), ucf:49799 (fedora) | |
| Note(s): |
2013-05-01 M.S. Medicine, Molecular Biology and Microbiology Masters This record was generated from author submitted information. |
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| Subject(s): | Streptozotocin -- Diabetes -- Diabetic Cardiomyopathy -- BMP-7 | |
| Persistent Link to This Record: | http://purl.flvc.org/ucf/fd/CFE0004765 | |
| Restrictions on Access: | campus 2016-05-15 | |
| Host Institution: | UCF |
