Endothelial microparticle-promoted inhibition of vascular remodeling is abrogated under hyperglycaemic conditions
Felix Jansen1, Andreas Zietzer1, Tobias Stumpf1
1Department of Internal Medicine II, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
Background:
Endothelial microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells.
Methods And Results:
EMPs were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMPs were defined as 'hyperglycaemic' EMPs (hgEMPs) and their miRNA transfer capacity and functional effects were compared with EMPs generated from 'healthy' untreated HCAECs. In vitro, the intercellular transfer of antiproliferative miRNA-126-3p from ECs to VSMCs via EMPs was significantly reduced under hyperglycaemic conditions. Additionally, EMP-mediated inhibition of the miRNA-126-3p target LRP6 and of VSMC migration and proliferation was abrogated, when hgEMPs were used. In vivo, the inhibitory effect of EMPs on neointima formation, VSMC proliferation and macrophage infiltration was abolished in mice treated with hgEMPs.
Conclusion:
Pathological hyperglycaemic conditions weaken potentially protective intercellular communication mechanisms by affecting EMP content and function.
Insights
Diabetic conditions impair endothelial microparticles (EMPs) ability to transfer protective microRNA-126-3p to smooth muscle cells, hindering their anti-remodeling effects. This dysfunction contributes to vascular complications in diabetes mellitus.
Area of Science:
- Vascular Biology
- Endocrinology
- Cellular Communication
Background:
- Endothelial microparticles (EMPs) are crucial for intercellular communication, regulating vascular remodeling via microRNA (miRNA) transfer.
- Elevated EMPs in diabetes mellitus suggest a link to vascular complications.
- The impact of high glucose on EMP function and miRNA transfer remains unclear.
Purpose of the Study:
- To investigate how high glucose conditions affect EMPs' miRNA transfer capacity and functional role in vascular remodeling.
- To compare the effects of EMPs from high glucose-exposed cells (hgEMPs) versus healthy cells.
Main Methods:
- EMPs were generated from human coronary artery endothelial cells (HCAECs) cultured under high glucose (mimicking diabetes) or normal conditions.
- In vitro studies assessed miRNA-126-3p transfer, target gene (LRP6) inhibition, and vascular smooth muscle cell (VSMC) migration/proliferation.
- In vivo studies evaluated the effect of hgEMPs on neointima formation, VSMC proliferation, and macrophage infiltration in mice.
Main Results:
- High glucose significantly reduced miRNA-126-3p transfer from ECs to VSMCs via EMPs.
- hgEMPs failed to inhibit the miRNA-126-3p target LRP6 and abrogated VSMC migration and proliferation.
- In vivo, hgEMPs lost their inhibitory effect on neointima formation, VSMC proliferation, and macrophage infiltration.
Conclusions:
- Pathological hyperglycemia impairs EMPs' protective function by altering their miRNA content and intercellular communication capabilities.
- This dysfunction contributes to vascular complications observed in diabetes mellitus.
- Targeting EMP function may offer therapeutic strategies for diabetic vascular disease.
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