by Tang, Jun, Lobatto, Mark E, Hassing, Laurien, van der Staay, Susanne, van Rijs, Sarian M, Calcagno, Claudia, Braza, Mounia S, Baxter, Samantha, Fay, Francois, Sanchez-Gaytan, Brenda L, Duivenvoorden, Raphaël, Sager, Hendrik B, Astudillo, Yaritzy M, Leong, Wei, Ramachandran, Sarayu, Storm, Gert, Pérez-Medina, Carlos, Reiner, Thomas, Cormode, David P, Strijkers, Gustav J, Stroes, Erik S G, Swirski, Filip K, Nahrendorf, Matthias, Fisher, Edward A, Fayad, Zahi A and Mulder, Willem J M
Abstract:

Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein Etextendashdeficient mice (Apoetextminus/textminus) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.

Reference:
Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation (Tang, Jun, Lobatto, Mark E, Hassing, Laurien, van der Staay, Susanne, van Rijs, Sarian M, Calcagno, Claudia, Braza, Mounia S, Baxter, Samantha, Fay, Francois, Sanchez-Gaytan, Brenda L, Duivenvoorden, Raphaël, Sager, Hendrik B, Astudillo, Yaritzy M, Leong, Wei, Ramachandran, Sarayu, Storm, Gert, Pérez-Medina, Carlos, Reiner, Thomas, Cormode, David P, Strijkers, Gustav J, Stroes, Erik S G, Swirski, Filip K, Nahrendorf, Matthias, Fisher, Edward A, Fayad, Zahi A and Mulder, Willem J M), In Science Advances, American Association for the Advancement of Science, volume 1, 2015.
Bibtex Entry:
@article{Storm:2015th,
author = {Tang, Jun and Lobatto, Mark E and Hassing, Laurien and van der Staay, Susanne and van Rijs, Sarian M and Calcagno, Claudia and Braza, Mounia S and Baxter, Samantha and Fay, Francois and Sanchez-Gaytan, Brenda L and Duivenvoorden, Rapha{"e}l and Sager, Hendrik B and Astudillo, Yaritzy M and Leong, Wei and Ramachandran, Sarayu and Storm, Gert and P{'e}rez-Medina, Carlos and Reiner, Thomas and Cormode, David P and Strijkers, Gustav J and Stroes, Erik S G and Swirski, Filip K and Nahrendorf, Matthias and Fisher, Edward A and Fayad, Zahi A and Mulder, Willem J M},
title = {{Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation}},
journal = {Science Advances},
year = {2015},
volume = {1},
number = {3},
pages = {e1400223--e1400223},
month = apr,
publisher = {American Association for the Advancement of Science},
doi = {10.1126/sciadv.1400223},
language = {English},
rating = {0},
date-added = {2017-08-22T11:03:17GMT},
date-modified = {2018-03-16T13:14:13GMT},
abstract = {<p>Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E{textendash}deficient mice (<i>Apoe</i><sup>{textminus}/{textminus}</sup>) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.</p>},
url = {http://advances.sciencemag.org/cgi/doi/10.1126/sciadv.1400223},
uri = {url{papers3://publication/doi/10.1126/sciadv.1400223}}
}