Big Congrats 🎉 to Rui Li & collaborators from the lab of Stefan Offermanns at @mpi_hlr
for this great #NatureComms paper showing that FAT1 controls YAP/TAZ degradation via the E3 ligase MIB2 during #angiogenesis.
Happy of my small contribution!
https://doi.org/10.1038/s41467-023-37671-x
IL-11 as a therapeutic target for lung #Fibrosis #Emphysema in #MarfanSyndrome
In Marfan🐭🫁, IL11-GFP reporter is active in #EndothelialCell #SmoothMuscleCell Fibroblast but not alveolar epithelia
Dr. Stuart A Cook & Wei Wen Lim lab ATVB 2023
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318802
Also don't miss the story on IL-11 as mediator of Mafan #Aortopathy from Circ Res 2022
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.320381
Human Meniscus single-cell RNAseq atlas
4 normal+4 #OsteoArthritis
5 #Chondroncyte subtypes
Emerging proliferative chondrocyte in degenerated tissue
OA-related #EndothelialCell/#MuralCell-Chondrocyte crosstalks🤓
Dr. W Fu & X Zhang labs @eLife 2023
https://elifesciences.org/articles/79585
Amh+ #SertoliCell is a major (80%) cellular source of #StemCellFactor in🐭Testis
Sertoli, Not #EndothelialCell SCF->
#Spermatogonia maintenance+differentiation
Cell-specific SCF Glycosylation? Proximity?🧐
Dr Hongfang Shao, Bo Zhou lab @Dev_journal 2023
https://journals.biologists.com/dev/article/doi/10.1242/dev.200706/293491/Sertoli-cells-are-the-unique-source-of-stem-cell
AP-1 transcription factors ATF3/FOSL1/FOSL2/c-JUN reshape Chromatin Accessibility landscape during #EndothelialCell #Senescence
HUVEC PD 8vs24vs36
1038 & 964 increased & decreased accessibility regions
>94% >2 kb from TSS
Dr. Wei Tao lab Aging Cell 2021
https://onlinelibrary.wiley.com/doi/10.1111/acel.13315
AP-1 TFs also play pioneering roles in fibroblast #Senescence 🤠
AP-1 imprints a reversible transcriptional programme of senescent cells
Dr. Oliver Bischof lab Nature Cell Bio 2020
https://www.nature.com/articles/s41556-020-0529-5
Low #OscillatoryShearStress->
⏫Osteopontin-CD44 in #EndothelialCell->
⏫EndMT->
⏫24% of neointimal cells at rat aortocaval junction
A cascade independent of #HyaluronicAcid🤓
Dr. Yung-Hsin Yeh lab Kidney Int 2023
https://www.kidney-international.org/article/S0085-2538(23)00011-X/fulltext
Single-nuclei Transcriptomics human Lung
#COVID19 x7
IPF x6
Ctrl x12
COVID🫁
⏫Systemic venous+capillary #EndothelialCell
⏬general capillary EC
⏬Epi-Endo Notch, EC-stromal PDGF
⏫Stromal-EC PlxnA-Sema3A
Dr. Peter Carmeliet lab #CardiovascRes 2022
https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvac139/6673943
Blood Vessel Organoids for Development & Disease
Self-organizing capillary blood vessel #Organoid #EndothelialCell+#Pericyte (+Astrocyte for #BBB)
Transplant to gain vascular hierarchy
Organotypism Through Genetic Drivers
Dr. Josef Penninger lab Circ Res 2023
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.122.321768
Aortic #Endotheliopathy #MarfanSyndrome
En face #EndothelialCell morphometry->
Alterations in EC shape/junction/alignment/eNOS Precede aortic dilation in Marfan🐭
Flow-sensing defect?😆
Dr. Vivian de Waard lab Scientific Reports 2023
https://www.nature.com/articles/s41598-022-26662-5
Mechano-vulnerability of #EndothelialCell in #Atherosclerosis 🤠
EVA1A, elevated by #DisturbedFlow-Twist1 axis, blocks EC #Autophagy & induces #Apoptosis
Dr. Paul Evans & Jovana Serbanovic-Canic lab ATVB 2023
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318110
Interesting to note that LC3B in EC +72 h #DisturbedFlow is mostly lipidated (Fig. 4A)
Does this suggest that endothelium under #DisturbedFlow enter an Autophagy-dependent state? For Survival, Shear-sensing & Secretion? 🧐
#EndothelialCell #Sirt6 deficiency->
⏫#TissueFactor/F3+vascular inflammation genes Cox2, VCAM1, TNFα, MCP1
Accelerated Carotid arterial #Thrombosis (Rose bengal)
A role in atherosclerotic plaque stability?😃
Dr. Christian Matter lab JMCC 2022
https://www.jmcc-online.com/article/S0022-2828(22)00565-X/fulltext
#LaminarShear pushes VE-PTP (How?🤓) to downstream pole of #EndothelialCell, followed by endocytosis->⏫p-Tie2
Potentially explain how #DisturbedFlow⏫#VascularPermeability & #Atherosclerosis
Inhibition of VE-PTP by AKB-9785 fortifies #EndothelialBarrier & reduces Atheromas at atheroprone regions (aortic arch inner curvature, arch+intercostal bifurcations)🐭
Nice comparison of anti-leakage strategies
VE-PTP inhibition
Angpt1 activation of Tie2
Angpt2 inhibition
Dr. Donald McDonald & Dietmar Vestweber labs EMBO Mol Med 2023
https://www.embopress.org/doi/
"Division of Labor" in Lung endothelial host defense 🐭#Endotoxemia 🐭#Influenza🐵#SARSCOV2
2 subsets of🫁general capillary #EndothelialCell
Irf7+ immune EC
Sox17+ developmental (regenerative) EC
Dr. Jalees Rehman lab JCI Insight 2022
https://insight.jci.org/articles/view/158079
Use Organoid to study Plasticity & Organotypic traits of #EndothelialCell
3D Cardiac Microtissue
#hiPSC-cardiomyocyte, -Fibroblast, -EC
scRNAseq
hiPSC-cardiac mesoderm-EC vs
hiPSC-Paraxial mesoderm-EC
in🫀Organoid
Dr. Valeria Orlova lab bioRxiv 2022
https://www.biorxiv.org/content/10.1101/2022.11.22.517426v2.full
Partial #EndMT,⏫by #Hypoxia-induced CD45, as a major cellular source for neointima formation
50% ECs in ligated artery are CD45+
CD45 is required to maintain this Partial status
Amazing!🤩
Dr. Yoshito Yamashiro & Yoshito Yamashiro lab #CardiovascRes 2022
https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvac190/6942105
How CD45 titrates the extent of mesenchymalization of #EndothelialCell?
CD45 stabilizes VE-cad junction via fortifying integrin α11-SHARPIN complex
Very interesting data on Biomechanics of #EndMT 😋
What (beyond CD45) control partial-to-complete EndMT transition?🤓
#Heme biosynthesis #Angigoenesis
Roles of #EndothelialCell FLVCR1a, a heme exporter to extracellular space in
✅Developmental Angiogenesis-🐭Retina🐟ISV
✅Tumor angiogenesis
❎Vascular homeostasis
Dr. Sara Petrillo lab Angiogenesis 2023
https://link.springer.com/article/10.1007/s10456-023-09865-w
FLVCR1a deficiency-> #EndothelialCell-autonomous defects in Mitochondria, ER stress & Angiogenic behaviors
Heme accumulation triggers #Paraptosis (Organelle swelling-> Cytoplasic vacuolation)💀
Dr. Emanuela Tolosano lab Cell Death Diff 2018
https://www.nature.com/articles/s41418-017-0001-7
Other enzymes in Heme metabolism in #Angiogensis👇
Ferrochelatase is a therapeutic target for ocular neovascularization
https://www.embopress.org/doi/full/10.15252/emmm.201606561
Serine Synthesis via PHGDH Is Essential for Heme Production in Endothelial Cells
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30391-7
Spatial analysis of Lung microvascular damage+regeneration, correlated with zoned alveolar damage following #Influenza injury
A critical role of #EndothelialCell COUP-TF2/Nr2f2
-Transcriptionally⏫CyclinD1+NRP1
-⏬by NFκB
Dr. Andrew Vaughan lab @vaughandy Science Advances 2020
https://www.science.org/doi/10.1126/sciadv.abc4493
#ThoracicAorticAneurysm
#EndothelialCell-#SmoothMuscleCell Synergy
EC Fbln4 KO exacerbates Aortopathy of SMC Fbln4 KO
-Aneurysm into Arch
-Descending Aortic tortuosity
-Postnatal aortic valve thickening/#EndMT
Dr. Yoshito Yamashiro and Hiromi Yanagisawa labs JAHA2022
https://www.ahajournals.org/doi/10.1161/JAHA.122.026942
Tie2+ #EndothelialCell Egln1/PHD2 KO mice
->Spontaneous #PulmonaryArterialHypertension as early as 1.5 mo
A cascade of EC PHD2 KO->
⏫autocrine #CXCL12->
⏫FoxM1-dependent proliferation
Dr. Zhiyu Dai lab IJMS_MDPI 2021
https://www.mdpi.com/1422-0067/22/6/3182
Also read Dr. Dai Circulation 2016🤠presenting EC PHD2 KO, causing PAH via HIF2α (not HIF1α)
PHD2 Deficiency in Endothelial Cells & Hematopoietic Cells Induces Obliterative Vascular Remodeling & Severe Pulmonary Arterial Hypertension PAH in🐭👤Through HIF2α
https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.116.021494
Endotheliopathy #CysticFibrosis
CFTR-deficient #EndothelialCell
⏫Inflammation IL8/SELE/ICAM1/VCAM1
⏬Proliferation
⏬Autophagy
⏬Barrier
⏫Mitochodriopathy
Dr. Lucas Treps, Guy Eelen, Peter Witters labs Eur Respir J 2021
https://erj.ersjournals.com/content/57/4/2000261.long
