Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit
Both IL-10 and STAT3 are in the same signal transduction pathway, with IL-10-bound IL10 receptor (R) acting through STAT3 for anti-inflammatory effect. To investigate possible therapeutic synergism, we delivered both full-length wild-type human (h) STAT3 and hIL-10 genes by separate adenoassociated...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Vascular Medicine |
| Online Access: | http://dx.doi.org/10.1155/2012/524235 |
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| author | Maohua Cao Junaid A. Khan Bum-Yong Kang Jawahar L. Mehta Paul L. Hermonat |
| author_facet | Maohua Cao Junaid A. Khan Bum-Yong Kang Jawahar L. Mehta Paul L. Hermonat |
| author_sort | Maohua Cao |
| collection | DOAJ |
| description | Both IL-10 and STAT3 are in the same signal transduction pathway, with IL-10-bound IL10 receptor (R) acting through STAT3 for anti-inflammatory effect. To investigate possible therapeutic synergism, we delivered both full-length wild-type human (h) STAT3 and hIL-10 genes by separate adenoassociated virus type 8 (AAV8) tail vein injection into LDLR KO on HCD. Compared to control Neo gene-treated animals, individual hSTAT3 and hIL-10 delivery resulted in significant reduction in atherogenesis, as determined by larger aortic lumen size, thinner aortic wall thickness, and lower blood velocity (all statistically significant). However, dual hSTAT3/hIL-10 delivery offered no improvement in therapeutic effect. Plasma cholesterol levels in dual hSTAT3/hIL-10-treated animals were statistically higher compared to hIL-10 alone. While no advantage was seen in this case, we consider that the dual gene approach has intrinsic merit, but properly chosen partnered genes must be used. |
| format | Article |
| id | doaj-art-7e31e0529abe471e9eb31f846211d811 |
| institution | Kabale University |
| issn | 2090-2824 2090-2832 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Vascular Medicine |
| spelling | doaj-art-7e31e0529abe471e9eb31f846211d8112025-02-03T05:52:50ZengWileyInternational Journal of Vascular Medicine2090-28242090-28322012-01-01201210.1155/2012/524235524235Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased BenefitMaohua Cao0Junaid A. Khan1Bum-Yong Kang2Jawahar L. Mehta3Paul L. Hermonat4Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USACentral Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USACentral Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USACentral Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USACentral Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USABoth IL-10 and STAT3 are in the same signal transduction pathway, with IL-10-bound IL10 receptor (R) acting through STAT3 for anti-inflammatory effect. To investigate possible therapeutic synergism, we delivered both full-length wild-type human (h) STAT3 and hIL-10 genes by separate adenoassociated virus type 8 (AAV8) tail vein injection into LDLR KO on HCD. Compared to control Neo gene-treated animals, individual hSTAT3 and hIL-10 delivery resulted in significant reduction in atherogenesis, as determined by larger aortic lumen size, thinner aortic wall thickness, and lower blood velocity (all statistically significant). However, dual hSTAT3/hIL-10 delivery offered no improvement in therapeutic effect. Plasma cholesterol levels in dual hSTAT3/hIL-10-treated animals were statistically higher compared to hIL-10 alone. While no advantage was seen in this case, we consider that the dual gene approach has intrinsic merit, but properly chosen partnered genes must be used.http://dx.doi.org/10.1155/2012/524235 |
| spellingShingle | Maohua Cao Junaid A. Khan Bum-Yong Kang Jawahar L. Mehta Paul L. Hermonat Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit International Journal of Vascular Medicine |
| title | Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit |
| title_full | Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit |
| title_fullStr | Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit |
| title_full_unstemmed | Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit |
| title_short | Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit |
| title_sort | dual aav il 10 plus stat3 anti inflammatory gene delivery lowers atherosclerosis in ldlr ko mice but without increased benefit |
| url | http://dx.doi.org/10.1155/2012/524235 |
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