Adventitial lymphatic capillary expansion impacts on plaque T cell accumulation in atherosclerosis

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Rademakers , T , van der Vorst , E P C , Daissormont , I T M N , Otten , J J T , Theodorou , K , Theelen , T L , Gijbels , M , Anisimov , A , Nurmi , H , Lindeman , J H N , Schober , A , Heeneman , S , Alitalo , K & Biessen , E A L 2017 , ' Adventitial lymphatic capillary expansion impacts on plaque T cell accumulation in atherosclerosis ' , Scientific Reports , vol. 7 , 45263 . https://doi.org/10.1038/srep45263

Title: Adventitial lymphatic capillary expansion impacts on plaque T cell accumulation in atherosclerosis
Author: Rademakers, Timo; van der Vorst, Emiel P. C.; Daissormont, Isabelle T. M. N.; Otten, Jeroen J. T.; Theodorou, Kosta; Theelen, Thomas L.; Gijbels, Marion; Anisimov, Andrey; Nurmi, Harri; Lindeman, Jan H. N.; Schober, Andreas; Heeneman, Sylvia; Alitalo, Kari; Biessen, Erik A. L.
Other contributor: University of Helsinki, University of Helsinki
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit



Date: 2017-03-28
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/srep45263
URI: http://hdl.handle.net/10138/188601
Abstract: During plaque progression, inflammatory cells progressively accumulate in the adventitia, paralleled by an increased presence of leaky vasa vasorum. We here show that next to vasa vasorum, also the adventitial lymphatic capillary bed is expanding during plaque development in humans and mouse models of atherosclerosis. Furthermore, we investigated the role of lymphatics in atherosclerosis progression. Dissection of plaque draining lymph node and lymphatic vessel in atherosclerotic ApoE(-/-)mice aggravated plaque formation, which was accompanied by increased intimal and adventitial CD3(+) T cell numbers. Likewise, inhibition of VEGF-C/D dependent lymphangiogenesis by AAV aided gene transfer of hVEGFR3-Ig fusion protein resulted in CD3(+) T cell enrichment in plaque intima and adventitia. hVEGFR3-Ig gene transfer did not compromise adventitial lymphatic density, pointing to VEGF-C/D independent lymphangiogenesis. We were able to identify the CXCL12/CXCR4 axis, which has previously been shown to indirectly activate VEGFR3, as a likely pathway, in that its focal silencing attenuated lymphangiogenesis and augmented T cell presence. Taken together, our study not only shows profound, partly CXCL12/CXCR4 mediated, expansion of lymph capillaries in the adventitia of atherosclerotic plaque in humans and mice, but also is the first to attribute an important role of lymphatics in plaque T cell accumulation and development.
Subject: APOLIPOPROTEIN E-DEFICIENT
DENDRITIC CELLS
VASA VASORUM
IN-VIVO
MICE
LESIONS
LYMPHANGIOGENESIS
PROMOTES
INFLAMMATION
PROGRESSION
3111 Biomedicine
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