التفاصيل البيبلوغرافية
| العنوان: |
HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs. |
| المؤلفون: |
Da Fonseca Ferreira, Andrea, Wei, Jianqin, Zhang, Lukun, Macon, Conrad J., Degnan, Bernard, Jayaweera, Dushyantha, Hare, Joshua M., Kolber, Michael A., Bellio, Michael, Khan, Aisha, Pan, Yue, Dykxhoorn, Derek M., Wang, Liyong, Dong, Chunming |
| المصدر: |
International Journal of Molecular Sciences; Apr2023, Vol. 24 Issue 8, p7567, 24p |
| مصطلحات موضوعية: |
EXTRACELLULAR vesicles, HIV, BONE marrow cells, HIV infections, MICRORNA, HIV-positive persons, IMMUNOSENESCENCE |
| مستخلص: |
People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIVneg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin− BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVneg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIVposEVs) and plasma depleted of EVs (HIV PLdepEVs). HIVposEVs, but not HIV PLdepEVs or HIVnegEVs (EVs from HIVneg individuals), increased atherosclerosis in apoE−/− mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin− BMCs. Small RNA-seq identified EV-miRs overrepresented in HIVposEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVposEVs in vivo. Lin− BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3′UTR and as such is resistant to miR-mediated regulation showed protection against HIVposEVs-induced changes in lin− BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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