Claudio Vinegoni, Ph.D. | RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction

Sci. Transl. Med.
RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction

Sager, H. B., Dutta, P., Dahlman, J. E., Hulsmans, M., Courties, G., Sun, Y., Heidt, T., Vinegoni, C., Borodovsky, A., Fitzgerald, K., Wojtkiewicz, G. R., Iwamoto, Y., Tricot, B., Khan, O. F., Kauffman, K. J., Xing, Y. P., Shaw, T. E., Libby, P., Langer, R., Weissleder, R., Swirski, F. K., Anderson, D. G., and Nahrendorf^#, M.

Science Translational Medicine 2016

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Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE(-/-) mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)-targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E-and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI.
@article{2016-STM, author= {Sager, H. B. and Dutta, P. and Dahlman, J. E. and Hulsmans, M. and Courties, G. and Sun, Y. and Heidt, T. and Vinegoni, C. and Borodovsky, A. and Fitzgerald, K. and Wojtkiewicz, G. R. and Iwamoto, Y. and Tricot, B. and Khan, O. F. and Kauffman, K. J. and Xing, Y. P. and Shaw, T. E. and Libby, P. and Langer, R. and Weissleder, R. and Swirski, F. K. and Anderson, D. G. and Nahrendorf<sup>#</sup>, M.}, title= {RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction}, journal= {Science Translational Medicine}, alternatejournal = {Sci. Transl. Med.}, year = {2016}, volume = {8}, number = {342}, pages = {11}, issn = {1946-6234}, doi = {10.1126/scitranslmed.aaf1435}, pmcid = {PMC5125383}, pmid= {27280687} }
27280687

PMC5125383

10.1126/scitranslmed.aaf1435

Abstract

"Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE(-/-) mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)-targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E-and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI."

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For attribution in academic contexts, please cite this work as:

Sager, H. B., Dutta, P., Dahlman, J. E., Hulsmans, M., Courties, G., Sun, Y., Heidt, T., Vinegoni, C., Borodovsky, A., Fitzgerald, K., Wojtkiewicz, G. R., Iwamoto, Y., Tricot, B., Khan, O. F., Kauffman, K. J., Xing, Y. P., Shaw, T. E., Libby, P., Langer, R., … Nahrendorf^#, M. (2016). RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Science Translational Medicine, 8(342), 11. https://doi.org/10.1126/scitranslmed.aaf1435