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International Journal of Vascular Medicine
Volume 2012, Article ID 524235, 7 pages
http://dx.doi.org/10.1155/2012/524235
Research Article

Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit

1Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USA
2Research of Cardiology, University of Arkansas for Medical Sciences and VA Medical Center, Little Rock, AR 72205, USA
3Department of Medicine, Atlanta Veterans Affairs and Emory University Medical Centers, Atlanta, GA 30033, USA

Received 25 April 2011; Accepted 20 June 2011

Academic Editor: Manuel Castro Cabezas

Copyright © 2012 Maohua Cao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.