CTHRSSVVC Peptide as a Possible Early Molecular Imaging Target for Atherosclerosis

Author(s):Show less -

Silva, Rosemeire A. ; Giordano, Ricardo J. ; Gutierrez, Paulo S. ; Rocha, Viviane Z. ; Rudnicki, Martina ; Kee, Patrick ; Abdalla, Dulcineia S. P. ; Puech-Leao, Pedro ; Caramelli, Bruno ; Arap, Wadih ; Pasqualini, Renata ; Meneghetti, Jose C. ; Marques, Fabio L. N. ; Khoobchandani, Menka ; Katti, Kattesh V. ; Lugao, Ademar B. ; Kalil, Jorge

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 17, n. 9, p. 18-pg., 2016-09-01.

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 (InCl3)-In-111 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. (AU)

• FAPESP's process: 04/02721-8 - Phage display and immune system: identification of molecular targets with diagnostic and therapeutic properties in immunological disorders
• Grantee: Jorge Elias Kalil Filho
• Support Opportunities: Research Projects - Thematic Grants