E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis

被引:136
作者
Ma, Shuangtao [1 ]
Tian, Xiao Yu [1 ,2 ,3 ]
Zhang, Yunrong [1 ]
Mu, Chaofeng [4 ]
Shen, Haifa [4 ]
Bismuth, Jean [5 ]
Pownall, Henry J. [1 ]
Huang, Yu [2 ,3 ]
Wong, Wing Tak [1 ]
机构
[1] Houston Methodist Res Inst, Dept Cardiovasc Sci, Houston, TX 77030 USA
[2] Chinese Univ Hong Kong, Sch Biomed Sci, Inst Vasc Med, Shatin, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China
[4] Houston Methodist Res Inst, Dept Nanomed, Houston, TX 77030 USA
[5] Houston Methodist Hosp, Methodist DeBakey Heart & Vasc Ctr, Houston, TX 77030 USA
关键词
IN-VIVO; ADHESION MOLECULES; NANOPARTICLES; FLOW; THERAPY; CELL; NEOVASCULARIZATION; INHIBITION;
D O I
10.1038/srep22910
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
E-selectin is a surface marker of endothelial cell (EC) inflammation, one of the hallmarks of atherogenesis. Thus, we tested the hypothesis that delivery of microRNA (miR)-146a and miR-181b with an E-selectin-targeting multistage vector (ESTA-MSV) to inflamed endothelium covering atherosclerotic plaques inhibits atherosclerosis. Cy5-conjugated miR-146a and miR-181b were packaged in polyethylene glycol-polyethyleneimine (PEG/PEI) nanoparticles and loaded into ESTA-MSV microparticles. Both miRs were downregulated in tumor necrosis factor (TNF)-alpha-treated ECs. Transfection of TNF-alpha-treated mouse aortas and cultured ECs with miRs was more efficient with ESTA-MSV than with the PEG/PEI. Likewise, miR-146a/-181b packaged in ESTA-MSV efficiently suppressed the chemokines, CCL2, CCL5, CCL8, and CXCL9, and monocyte adhesion to ECs. Complementary in vivo tests were conducted in male apolipoprotein E-deficient mice fed a Western diet and injected intravenously with the particles prepared as above biweekly for 12 weeks. Treatment with miRs packaged in ESTA-MSV but not in PEG/PEI reduced atherosclerotic plaque size. Concurrently, vascular inflammation markers, including macrophages in aortic root lesions and chemokine expression in aortic tissues were reduced while the vascular smooth muscle cells and collagen increased in plaques from ESTA-MSV/miRs-treated vs. vehicle-treated mice. Our data supported our hypothesis that ESTA-MSV microparticle-mediated delivery of miR-146a/-181b ameliorates endothelial inflammation and atherosclerosis.
引用
收藏
页数:11
相关论文
共 46 条
[21]   Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo [J].
Lewis, Daniel R. ;
Petersen, Latrisha K. ;
York, Adam W. ;
Zablocki, Kyle R. ;
Joseph, Laurie B. ;
Kholodovych, Vladyslav ;
Prud'homme, Robert K. ;
Uhrich, Kathryn E. ;
Moghe, Prabhas V. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (09) :2693-2698
[22]   Apolipoprotein E Enhances MicroRNA-146a in Monocytes and Macrophages to Suppress Nuclear Factor-κB-Driven Inflammation and Atherosclerosis [J].
Li, Kang ;
Ching, Daniel ;
Luk, Fu Sang ;
Raffai, Robert L. .
CIRCULATION RESEARCH, 2015, 117 (01) :e1-e11
[23]   Inflammation and atherosclerosis [J].
Libby, P ;
Ridker, PM ;
Maseri, A .
CIRCULATION, 2002, 105 (09) :1135-1143
[24]   Atherosclerotic Plaque Targeting Mechanism of Long-Circulating Nanoparticles Established by Multimodal Imaging [J].
Lobatto, Mark E. ;
Calcagno, Claudia ;
Millon, Antoine ;
Senders, Max L. ;
Fay, Francois ;
Robson, Philip M. ;
Ramachandran, Sarayu ;
Binderup, Tina ;
Paridaans, Maarten P. M. ;
Sensarn, Steven ;
Rogalla, Stephan ;
Gordon, Ronald E. ;
Cardoso, Luis ;
Storm, Gert ;
Metselaar, Josbert M. ;
Contag, Christopher H. ;
Stroes, Erik S. G. ;
Fayad, Zahi A. ;
Mulder, Willem J. M. .
ACS NANO, 2015, 9 (02) :1837-1847
[25]   Bone marrow endothelium-targeted therapeutics for metastatic breast cancer [J].
Mai, Junhua ;
Huang, Yi ;
Mu, Chaofeng ;
Zhang, Guodong ;
Xu, Rong ;
Guo, Xiaojing ;
Xia, Xiaojun ;
Volk, David E. ;
Lokesh, Ganesh L. ;
Thiviyanathan, Varatharasa ;
Gorenstein, David G. ;
Liu, Xuewu ;
Ferrari, Mauro ;
Shen, Haifa .
JOURNAL OF CONTROLLED RELEASE, 2014, 187 :22-29
[26]   Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer [J].
Malam, Yogeshkumar ;
Loizidou, Marilena ;
Seifalian, Alexander M. .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2009, 30 (11) :592-599
[27]   Neovascularization in human atherosclerosis [J].
Moreno, PR ;
Purushothaman, KR ;
Sirol, M ;
Levy, AP ;
Fuster, V .
CIRCULATION, 2006, 113 (18) :2245-2252
[28]   Nanoparticle-mediated delivery of therapeutic genes: focus on miRNA therapeutics [J].
Muthiah, Muthunarayanan ;
Park, In-Kyu ;
Cho, Chong-Su .
EXPERT OPINION ON DRUG DELIVERY, 2013, 10 (09) :1259-1273
[29]   In vivo evaluation of vascular-targeted spheroidal microparticles for imaging and drug delivery application in atherosclerosis [J].
Namdee, Katawut ;
Thompson, Alex J. ;
Golinski, Alexander ;
Mocherla, Supriya ;
Bouis, Diane ;
Eniola-Adefeso, Omolola .
ATHEROSCLEROSIS, 2014, 237 (01) :279-286
[30]   MicroRNAs in flow-dependent vascular remodelling [J].
Neth, Peter ;
Nazari-Jahantigh, Maliheh ;
Schober, Andreas ;
Weber, Christian .
CARDIOVASCULAR RESEARCH, 2013, 99 (02) :294-303