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Bone Marrow-Derived Alk1 Mutant Endothelial Cells and Clonally Expanded Somatic Alk1 Mutant Endothelial Cells Contribute to the Development of Brain Arteriovenous Malformations in Mice
AbstractWe have previously demonstrated that deletion of activin receptor-like kinase 1 (Alk1) or endoglin in a fraction of endothelial cells (ECs) induces brain arteriovenous malformations (bAVMs) in adult mice upon angiogenic stimulation. Here, we addressed three related questions: (1) couldAlk1− mutant bone marrow (BM)-derived ECs (BMDECs) cause bAVMs? (2) is Alk1− ECs clonally expended during bAVM development? and (3) is the number of mutant ECs correlates to bAVM severity? For the first question, we transplanted BM fromPdgfbiCreER;Alk12f/2f mice (EC-specific tamoxifen-inducible Cre withAlk1-floxed alleles) into wi...
Source: Translational Stroke Research - October 21, 2021 Category: Neurology Source Type: research
The role of microglial/macrophagic salt-inducible kinase 3 on normal and excessive phagocytosis after transient focal cerebral ischemia
This study is the first to show a role of SIK3 in Mi/MΦ phagocytosis in CNS diseases, and reveals that promoting Mi/MΦ anti-inflammatory heterogenization inhibits "excessive phagocytosis" of live cells and facilitates "normal phagocytosis" of apoptotic cells. Therefore, inhibition of SIK3 in Mi/MΦ may be a potential therapeutic target in stroke and other CNS diseases with accompanying white matter destruction. In the acute stage of tFCI, Mi/MΦ polarized into different phenotypes. The pro-inflammatory Mi/MΦ phenotype performed an excessive phagocytotic function. In contrast, the anti-inflammatory Mi/MΦ phenotype perfo...
Source: Cellular and Molecular Life Sciences : CMLS - July 21, 2022 Category: Cytology Authors: Ke Wang Chenran Wang Di Chen Yichen Huang Jiaying Li Pengju Wei Ziyu Shi Yue Zhang Yanqin Gao Source Type: research
Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling
The cytochrome P450 reductase (POR) transfers electrons to all microsomal cytochrome P450 enzymes (CYP450) thereby driving their activity. In the vascular system, the POR/CYP450 system has been linked to the production of epoxyeicosatrienoic acids (EETs) but also to the generation of reactive oxygen species. In cardiac myocytes (CMs), EETs have been shown to modulate the cardiac function and have cardioprotective effects. The functional importance of the endothelial POR/CYP450 system in the heart is unclear and was studied here using endothelial cell-specific, inducible knockout mice of POR (ecPOR−/−). RNA sequencing o...
Source: Frontiers in Physiology - December 2, 2022 Category: Physiology Source Type: research
GSE214776 Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling
Contributors : Melina Lopez ; Pedro F Malacarne ; Deepak P Ramanujam ; Timothy Warwick ; Niklas M üller ; Jiong Hu ; Matthias Dewenter ; Andreas Weigert ; Stefan Günther ; Ralf Gilsbach ; Stefan Engelhardt ; Ralf P Brandes ; Flávia RezendeSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe cytochrome P450 reductase (POR) transfers electrons to all microsomal cytochrome P450 enzymes (CYP450) thereby driving their activity. In the vascular system, the POR/CYP450 system has been linked to the production of epoxyeicosatrienoic acids (EETs) but also to the generation of reactive oxygen ...
Source: GEO: Gene Expression Omnibus - December 21, 2022 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
