Artikel
Doxycycline is a potential drug to reduce oxidative stress-induced expression of MMPs in endothelial cells
Doxycyclin als potentielles Medikament reduziert die Expression von MMPs nach oxidativem Stress
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Autoren
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Xuanchen Li
- Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
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Dilaware Khan
- Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
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Huakang Zhou
- Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
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Majeed Rana
- Universitätsklinikum Düsseldorf, Department of Oral and Maxillofacial Surgery, Düsseldorf, Deutschland
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Daniel Hänggi
- Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
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Sajjad Muhammad
- Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
| Veröffentlicht: | 25. Mai 2022 |
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Gliederung
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Objective: Oxidative stress increases the release of matrix metalloproteases (MMPs). MMPs via digesting extracellular matrix contribute strongly to aneurysm pathophysiology. In addition to other cell types, endothelial cells produce and release MMPs. In this study, we investigated the effects of Doxycycline on MMPs expression in human umbilical vein endothelial cells (HUVECs) after exposure to oxidative stress.
Methods: HUVECs (Promocell, Heidelberg, Germany) were treated with different concentrations (100µM, 200µM) of hydrogen peroxide (H2O2) with or without Doxcycline (2µg/mL). The relative mRNAs expression of a panel of MMPs was quantified by qRT-PCR. All experiments were performed with three biological replicates and each biological replicate had technical triplicates. For statistical analysis, the Student t-test was applied for two groups and one-way ANOVA to compare more than two groups.
Results: H2O2 increased relative mRNA expression of multiple MMPs in HUVECs: MMP-1 (Control=1±0.25, H2O2=9.2±0.9), MMP-2 (Control=1±0.07, H2O2=1.76±0.08), MMP-8 (Control=1±0.08, H2O2=1.72±0.2), MMP-10 (Control=1±0.15, H2O2=5.35±0.3) and MMP-11 (Control=1±0.19, H2O2=2.54±0.47). Doxcycline reduced oxidative stress induced mRNA expression of MMPs (MMP-1: Control=1±0.25, H2O2=9.2±0.9, H2O2 + Doxcycline=5.09±0.5; MMP-2: Control=1±0.07, H2O2=1.76±0.08, H2O2 + Doxcycline=1.18±0.08; MMP-8: Control=1±0.08, H2O2=1.72±0.2, H2O2 + Doxcycline=1.18±0.23; MMP-10: Control=1±0.15, H2O2=5.35±0.3, H2O2 + Doxcycline=3.85±0.27 and MMP-11: Control=1±0.19, H2O2=2.54±0.47, H2O2 + Doxcycline=1.74±0.18). All values are mean±StDev and P<0.05.
Conclusion: Doxycycline reduced the MMPs expression in HUVECs induced by oxidative stress. We propose doxycycline as a potential candidate to ameliorate oxidative stress-mediated MMPs expression in vascular diseases.
