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Published on: November 17, 2017
MiR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression,
Donald Ho1, Tyler O Lynd2, Claire Jun3
1Department of Pediatric Dentistry, University of Alabama at Birmingham, AL, 35294, USA.
Abstract:
Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κβ) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses. First, the miR-146a encapsulated liposomes showed uniform size (radius 96.4 ± 4.22 nm) and round shape, long term stability (at least two months), high encapsulation efficiency (69.73 ± 0.07%), and were well transfected to human aortic endothelial cells (HAECs), human aortic smooth muscle cells (SMCs), and human differentiated monocytes (U937 cells). In addition, we demonstrated that miR-146a encapsulated liposomes reduced vascular inflammation responses in HAECs and SMCs through inhibition of ICAM-1 expression and decreased monocyte adhesion. In macrophages, miR-146a liposome treatment demonstrated decreased production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), as well as reduced oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation. Thus, based on these results, miR-146a encapsulated liposomes may be promising for reducing vascular inflammation by targeting its multiple associated mediators.
Insights
Liposomes delivering microRNA 146a (miR-146a) effectively reduced vascular inflammation in cells. This targeted approach shows promise for treating inflammatory vascular diseases like atherosclerosis.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Cardiovascular Research
Background:
- Vascular insults trigger inflammatory responses involving endothelial cells, smooth muscle cells, and macrophages, contributing to atherosclerosis.
- MicroRNA 146a (miR-146a) exhibits anti-inflammatory properties by regulating the nuclear factor kappa beta (NF-κβ) pathway.
Purpose of the Study:
- To investigate the therapeutic potential of exogenous miR-146a encapsulated in liposomes for mitigating vascular inflammation.
- To assess the efficacy of miR-146a liposomes in reducing inflammatory markers and cellular responses in stimulated vascular cells and macrophages.
Main Methods:
- Liposomes were engineered for uniform size, stability, and high encapsulation efficiency of miR-146a.
- Transfection efficiency of miR-146a liposomes in human aortic endothelial cells (HAECs), smooth muscle cells (SMCs), and U937 monocytes was confirmed.
- Inflammatory responses, including ICAM-1 expression, monocyte adhesion, pro-inflammatory cytokine production (TNF-α, IL-1β), oxidized low-density lipoprotein (ox-LDL) uptake, and foam cell formation were measured.
Main Results:
- miR-146a liposomes demonstrated successful transfection and were stable.
- Treatment reduced vascular inflammation in HAECs and SMCs by inhibiting ICAM-1 and decreasing monocyte adhesion.
- In macrophages, miR-146a liposomes suppressed pro-inflammatory cytokines, reduced ox-LDL uptake, and inhibited foam cell formation.
Conclusions:
- Exogenous miR-146a encapsulated in liposomes effectively reduces multiple inflammatory mediators in vascular cells and macrophages.
- miR-146a liposomes represent a promising therapeutic strategy for managing inflammatory vascular diseases, including atherosclerosis.
