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Int. J. Mol. Sci. 2016, 17(9), 1383; doi:10.3390/ijms17091383

CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis

1
Laboratory of Immunology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
2
Chemistry Institute, Biochemistry Department, University of Sao Paulo, Sao Paulo 05508-000, Brazil
3
Laboratory of Pathology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
4
Clinical Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
5
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences University of São Paulo, São Paulo 05508-000, Brazil
6
Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA
7
Division of Vascular and Endovascular Surgery, University of São Paulo Medical School, São Paulo 05403-000, Brazil
8
University of New Mexico Comprehensive Cancer Center, Division of Hematology/Oncology and Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine Albuquerque, NM 87131, USA
9
Medicine Nuclear Service and Molecular Image, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil
10
Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo (LIM43), São Paulo 05403-911, Brazil
11
Institute of Green Nanotechnology, Department of Radiology and Chemistry, University of Missouri, Columbia, MO 65211, USA
12
Nuclear and Energy Research Institute—IPEN/CNEN/São Paulo 05508-000, Brazil
*
Authors to whom correspondence should be addressed.
Academic Editor: Már Másson
Received: 23 June 2016 / Revised: 16 August 2016 / Accepted: 16 August 2016 / Published: 24 August 2016
(This article belongs to the Special Issue Drug Delivery and Antimicrobial Agents)
View Full-Text   |   Download PDF [4237 KB, uploaded 24 August 2016]   |  

Abstract

The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05), when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR) domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr−/−) mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC) was synthesized and labeled with 111InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases. View Full-Text
Keywords: atherosclerosis; CD163; macrophages; theranostics; peptide atherosclerosis; CD163; macrophages; theranostics; peptide
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MDPI and ACS Style

Silva, R.A.; Giordano, R.J.; Gutierrez, P.S.; Rocha, V.Z.; Rudnicki, M.; Kee, P.; Abdalla, D.S.P.; Puech-Leão, P.; Caramelli, B.; Arap, W.; Pasqualini, R.; Meneghetti, J.C.; Marques, F.L.N.; Khoobchandani, M.; Katti, K.V.; Lugão, A.B.; Kalil, J. CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis. Int. J. Mol. Sci. 2016, 17, 1383.

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