title: CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis.
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 (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.
authors: 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.
authors: Rosemeire A
authors: RA
authors: Silva
authors: Chemistry Institute, Biochemistry Department, University of Sao Paulo, Sao Paulo 05508-000, Brazil. giordano@iq.usp.br.
authors: Ricardo J
authors: RJ
authors: Giordano
authors: 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.
authors: Paulo S
authors: PS
authors: Gutierrez
authors: 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.
authors: Viviane Z
authors: VZ
authors: Rocha
authors: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences University of São Paulo, São Paulo 05508-000, Brazil. martina.rudnicki@gmail.com.
authors: Martina
authors: M
authors: Rudnicki
authors: 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.
authors: Patrick
authors: P
authors: Kee
authors: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences University of São Paulo, São Paulo 05508-000, Brazil. dspabdalla@gmail.com.
authors: Dulcinéia S P
authors: DS
authors: Abdalla
authors: Division of Vascular and Endovascular Surgery, University of São Paulo Medical School, São Paulo 05403-000, Brazil. pedro@puech.com.br.
authors: Pedro
authors: P
authors: Puech-Leão
authors: 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.
authors: Bruno
authors: B
authors: Caramelli
authors: 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.
authors: Wadih
authors: W
authors: Arap
authors: 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.
authors: Renata
authors: R
authors: Pasqualini
authors: 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.
authors: José C
authors: JC
authors: Meneghetti
authors: Departamento de Radiologia e Oncologia, Faculdade de Medicina da Universidade de São Paulo (LIM43), São Paulo 05403-911, Brazil. fabio.marques@fm.usp.br.
authors: Fabio L N
authors: FL
authors: Marques
authors: Institute of Green Nanotechnology, Department of Radiology and Chemistry, University of Missouri, Columbia, MO 65211, USA. khoobchandanim@health.missouri.edu.
authors: Menka
authors: M
authors: Khoobchandani
authors: Institute of Green Nanotechnology, Department of Radiology and Chemistry, University of Missouri, Columbia, MO 65211, USA. kattik@health.missouri.edu.
authors: Kattesh V
authors: KV
authors: Katti
authors: Nuclear and Energy Research Institute-IPEN/CNEN/São Paulo 05508-000, Brazil. ablugao@gmail.com.
authors: Ademar B
authors: AB
authors: Lugão
authors: 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.
authors: Jorge
authors: J
authors: Kalil
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry; D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism; D004195:Disease Models, Animal; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D010455:Peptides; D011956:Receptors, Cell Surface; D011973:Receptors, LDL
keywords: CD163; atherosclerosis; macrophages; peptide; theranostics