Dataset Information

MnTBAP increases BMPR-II expression in endothelial cells and attenuates vascular inflammation.

ABSTRACT:

Aims

The endothelium plays an important role during vascular inflammation. Previous data have demonstrated a high expression level of manganese-superoxide dismutase (MnSOD) in endothelial cells and suggested an important role of MnSOD in several cardiovascular diseases. Manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD and prevented the development of diabetes and obesity. However, its effect on vascular inflammation and the underlying mechanism is still unknown.

Methods and results

Leukocyte adhesion was evaluated in-vivo and in-vitro using dynamic flow chamber and intravital microscopy in mice. Expression of adhesion molecules induced by TNFα and adhesion of leukocytes to the vessel wall were inhibited by MnTBAP. The anti-inflammatory effect of MnTBAP was partly mediated by up-regulation of the BMPR-II and Smad dependent pathway. Additionally, MnTBAP decelerated the turn-over of endogenous BMPR-II.

Conclusion

Our data demonstrate that MnTBAP activates Smad signaling, preserves the turn-over of BMPR-II and elicits anti-inflammatory effects in endothelial cells, partly mediated by BMPR-II. This finding suggests a potential therapeutic impact of MnTBAP in the treatment of vascular inflammation.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC5563469 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

MnTBAP increases BMPR-II expression in endothelial cells and attenuates vascular inflammation.

Zhou Qian Q Einert Michaela M Schmitt Hannah H Wang Zhengguan Z Pankratz Franziska F Olivier Christoph B CB Bode Christoph C Liao James K JK Moser Martin M

Vascular pharmacology 20160708

<h4>Aims</h4>The endothelium plays an important role during vascular inflammation. Previous data have demonstrated a high expression level of manganese-superoxide dismutase (MnSOD) in endothelial cells and suggested an important role of MnSOD in several cardiovascular diseases. Manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) has been shown to mimic some of the effects of MnSOD and prevented the development of diabetes and obesity. However, its effect on vascular inflammation and the ...[more]

PMID: 27401963

Similar Datasets

Project description:Aims To investigate whether DNA active demethylase TET regulates the expression of tight junction proteins in endothelial cells of the blood–brain barrier (BBB). Methods Correlations between TET2 activity (indicated by its catalytic product 5hmC) and the expression of BBB tight junction proteins were examined in Tet2 knockout mice and post-mortem human brain tissues. In cultured endothelial cells, the impact of changes of TET activity on the expression of tight junction protein, ZO-1, was studied. BBB permeability assays were performed in Tet2 knockout mice. Results It was found that the level of 5hmC decreased in brain microvascular endothelial cells of aging mice. In Tet2 knockout mice, the level of 5hmC in endothelial cells was weaker and significantly correlated with the reduced expression of tight junction protein ZO-1. In cultured endothelial cells, H2O2 significantly decreased the expression of 5hmC and ZO-1. Tet2 knock-down using siRNA significantly downregulated the expression of ZO-1 in endothelial cells. hMeChip-PCR showed that H2O2 decreased the level of 5hmC in the ZO-1 promoter region, which was rescued by N-acetyl cysteine (NAC). Consistently, Tet2 knock-down using siRNA significantly downregulated the level of 5hmC in the ZO-1 promoter region. It was also found that the level of 5hmC decreased in endothelial cells of aging human brains compared with that of adult brains, and the level of ZO-1 was positively correlated with that of 5hmC in microvascular endothelial cells. Conclusions These findings suggest that TET activity is essential in regulating ZO-1 expression of BBB. It might be a potential target for neuroprotection during aging and in diverse neurological conditions. Supplementary Information The online version contains supplementary material available at 10.1186/s12987-022-00370-8. Keypoints The expression of tight junction protein ZO-1 decreased significantly in the aged human brain. TET activity of cerebral endothelial cells declines during aging. TET activity is essential in regulating the expression of ZO-1 by endothelial cells of BBB. Supplementary Information The online version contains supplementary material available at 10.1186/s12987-022-00370-8.

Dataset Information

MnTBAP increases BMPR-II expression in endothelial cells and attenuates vascular inflammation.

Aims

Methods and results

Conclusion

Publications

MnTBAP increases BMPR-II expression in endothelial cells and attenuates vascular inflammation.

Similar Datasets

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