CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis.

Autor: Silva RA; Laboratory of Immunology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil. uitroseme@gmail.com., Giordano RJ; Chemistry Institute, Biochemistry Department, University of Sao Paulo, Sao Paulo 05508-000, Brazil. giordano@iq.usp.br., Gutierrez PS; Laboratory of Pathology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil. paulo.gutierrez@incor.usp.br., Rocha VZ; Clinical Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil. vzrocha@hotmail.com., Rudnicki M; Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences University of São Paulo, São Paulo 05508-000, Brazil. martina.rudnicki@gmail.com., Kee P; Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA. patrick.kee@uth.tmc.edu., Abdalla DS; Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences University of São Paulo, São Paulo 05508-000, Brazil. dspabdalla@gmail.com., Puech-Leão P; Division of Vascular and Endovascular Surgery, University of São Paulo Medical School, São Paulo 05403-000, Brazil. pedro@puech.com.br., Caramelli B; Clinical Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil. bcaramel@usp.br., Arap W; 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. warap@salud.unm.edu., Pasqualini R; 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. rpasqual@salud.unm.edu., Meneghetti JC; 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. meneghetti@incor.usp.br., Marques FL; Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo (LIM43), São Paulo 05403-911, Brazil. fabio.marques@fm.usp.br., Khoobchandani M; Institute of Green Nanotechnology, Department of Radiology and Chemistry, University of Missouri, Columbia, MO 65211, USA. khoobchandanim@health.missouri.edu., Katti KV; Institute of Green Nanotechnology, Department of Radiology and Chemistry, University of Missouri, Columbia, MO 65211, USA. kattik@health.missouri.edu., Lugão AB; Nuclear and Energy Research Institute-IPEN/CNEN/São Paulo 05508-000, Brazil. ablugao@gmail.com., Kalil J; Laboratory of Immunology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil. jkalil@usp.br.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2016 Aug 24; Vol. 17 (9). Date of Electronic Publication: 2016 Aug 24.
DOI: 10.3390/ijms17091383
Abstrakt: 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 (111)InCl₃ 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.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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