Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination.
W, S., W, L., M, G., T, Y., Y, W., T, W., S, L., X, X., Y, J., & Q, D. (2026). Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination.. Journal of extracellular vesicles. https://doi.org/10.1002/jev2.70319
W S, W L, M G, T Y, Y W, T W, et al. Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination.. Journal of extracellular vesicles. 2026; doi: 10.1002/jev2.70319
W S, W L, M G, et al. Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination.[J]. Journal of extracellular vesicles. 2026. DOI: 10.1002/jev2.70319.
@article{w2026,
author = {Shen W and Liu W and Guo M and You T and Wang Y and Wen T and Liang S and Xie X and Jiang Y and Dong Q},
title = {Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination.},
journal = {Journal of extracellular vesicles},
year = {2026},
doi = {10.1002/jev2.70319},
note = {PMID: 42226579},
}
TY - JOUR AU - Shen W AU - Liu W AU - Guo M AU - You T AU - Wang Y AU - Wen T AU - Liang S AU - Xie X AU - Jiang Y AU - Dong Q TI - Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination. T2 - Journal of extracellular vesicles PY - 2026 DO - 10.1002/jev2.70319 AN - PMID:42226579 ER -
Pericyte dysfunction is an early hallmark of vascular cognitive impairment (VCI), yet targeted therapies remain limited. Here, we develop a bio-orthogonal approach to engineer extracellular vesicles (EVs) functionalized with cyclic NGR (cNGR) peptides for selective pericytes targeting. The resulting cNGR-EVs demonstrated efficient targeting of CD13-expressing brain pericytes both in vitro and in vivo. In a mouse model of chronic cerebral hypoperfusion (bilateral common carotid artery stenosis, BCAS), cNGR-EVs preserved pericyte contractility, protected against cerebral hypoperfusion, reduced blood-brain barrier leakage, and attenuated demyelination, leading to improved cognitive performance. Single-cell RNA sequencing further revealed that cNGR-EVs attenuated the majority of BCAS-induced transcriptional changes in pericytes, partially preserved pericyte-mediated intercellular communication, and normalized downstream neuronal and glial gene expression profiles. These findings underscore cNGR-EVs as a pericyte-targeted strategy capable of stabilizing the neurovascular unit, maintaining pericyte function, and preventing cognitive decline and myelin loss, highlighting pericytes as a promising therapeutic target in early VCI treatment.