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Extracellular Vesicles from Caveolin-Enriched Microdomains Regulate Hyaluronan-Mediated Sustained Vascular Integrity
Tamara Mirzapoiazova1, Frances E Lennon2, Bolot Mambetsariev1
1Department of Medicine, Section of Pulmonary and Critical Care, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
International Journal of Cell Biology
|October 9, 2015
Summary
High molecular weight hyaluronan (HMW-HA) enhances vascular barrier integrity via specialized enlargeosomes. Low molecular weight hyaluronan (LMW-HA) disrupts it through exosomes, revealing distinct extracellular vesicle roles in vascular health.
Area of Science:
- Cell Biology
- Biochemistry
- Vascular Biology
Background:
- Vascular integrity defects initiate disease.
- High molecular weight hyaluronan (HMW-HA) enhances endothelial barrier function.
- Low molecular weight hyaluronan (LMW-HA) disrupts endothelial barrier function.
Purpose of the Study:
- To elucidate mechanisms of sustained hyaluronan (HA)-mediated vascular barrier regulation.
- To investigate the role of extracellular vesicles in HA-induced barrier modulation.
- To differentiate the effects of HMW-HA and LMW-HA on endothelial cells.
Main Methods:
- Long-term exposure of human pulmonary microvascular endothelial cells (HPMVEC) to HMW-HA and LMW-HA.
- Analysis of extracellular vesicle release (enlargosomes and exosomes).
- Inhibition of caveolin-enriched microdomain (CEM) formation and annexin II.
- Assessment of HPMVEC barrier function upon exposure to isolated extracellular vesicles.
Main Results:
- HMW-HA induced enlargeosome release; LMW-HA induced exosome release.
- Extracellular vesicle release was dependent on CEM formation.
- Inhibition of enlargeosome release attenuated HMW-HA's barrier-enhancing effect.
- Enlargeosomes enhanced barrier function; exosomes disrupted it.
Conclusions:
- Differential extracellular vesicle release from CEM modulates sustained HPMVEC barrier regulation by HA.
- HMW-HA-induced enlargeosomes represent a potential therapeutic strategy for vascular integrity diseases.
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