Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-09-25

AUTHORS

T Nomoto, T Okada, K Shimazaki, T Yoshioka, M Nonaka-Sarukawa, T Ito, K Takeuchi, K-i Katsura, H Mizukami, A Kume, S Ookawara, U Ikeda, Y Katayama, K Ozawa

ABSTRACT

Interleukin-10 (IL-10) ameliorates various T-helper type 1 cell-mediated chronic inflammatory diseases. Although the therapeutic benefits of IL-10 include antiatherosclerotic effects, pathophysiological effects of IL-10 on vascular remodeling in hypertension have not yet been elucidated. These studies were designed to determine whether sustained IL-10 expression, mediated by an adeno-associated virus (AAV) vector, prevents vascular remodeling and target-organ damage in the stroke-prone spontaneously hypertensive rat (SHR-SP)—an animal model of malignant hypertension. A single intramuscular injection of an AAV1 vector encoding rat IL-10 introduced long-term IL-10 expression. These IL-10-transduced rats had decreased stroke episodes and proteinuria, resulting in improved survival. Histological examination revealed a reduced level of deleterious vascular remodeling of resistance vessels in the brain and kidney of these rats. Immunohistochemical analysis indicated that IL-10 inhibited the enhanced renal transforming growth factor-β expression and perivascular infiltration of monocytes/macrophages and nuclear factor-κB-positive cells normally observed in the SHR-SP. Four weeks after IL-10 vector injection, systolic blood pressure significantly decreased and this effect persisted for several months. Overall, AAV vector-mediated systemic IL-10 expression prevented vascular remodeling and inflammatory lesions of target organs in the SHR-SP. This approach provides significant insights into the prevention strategy of disease onset with unknown genetic predisposition or intractable polygenic disorders. More... »

PAGES

383-391

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gt.2008.151

DOI

http://dx.doi.org/10.1038/gt.2008.151

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017661140

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18818668


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77 monocytes/macrophages
78 months
79 onset
80 organs
81 pathophysiological effects
82 perivascular infiltration
83 polygenic disorder
84 positive cells
85 predisposition
86 pressure
87 prevention strategies
88 proteinuria
89 rat IL-10
90 rats
91 remodeling
92 renal transforming growth
93 resistance vessels
94 significant insights
95 single intramuscular injection
96 strategies
97 stroke episode
98 study
99 survival
100 systemic delivery
101 systolic blood pressure
102 target organ damage
103 target organs
104 therapeutic benefit
105 unknown genetic predisposition
106 vascular remodeling
107 vector
108 vector injection
109 vessels
110 virus vectors
111 weeks
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