A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina.
Fenny H F TangFernanda I StaquiciniAndré A R TeixeiraJussara S MichaloskiGislene M NamiyamaNoemi N TaniwakiJoão C SetubalAline M da SilvaRichard L SidmanRenata PasqualiniWadih ArapRicardo Jose GiordanoPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine-Arginine-Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.
Keyphrases
- optic nerve
- endothelial cells
- resting state
- amino acid
- white matter
- functional connectivity
- single molecule
- high resolution
- gene expression
- cerebral ischemia
- public health
- healthcare
- pseudomonas aeruginosa
- nitric oxide
- mental health
- optical coherence tomography
- cystic fibrosis
- mesenchymal stem cells
- climate change
- mass spectrometry
- brain injury
- risk assessment
- human health
- fluorescence imaging
- blood brain barrier