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

#ArterioVenousFistula #EndMT

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

#Angiocrine #AlveolarRegeneration

P.aeruginosa Lung injury,🐭#EndothelialCell KO of Sphk1, S1P-generating enzyme->
Excess Sftpc-hi AT2
AT1 loss & airspace enlargement

S1P/S1PR2⏫#YAP nucleation->⏫AT2-to-AT1 differentiation

Dr. Yuru Liu lab Cell Reports 2020
https://www.sciencedirect.com/science/article/pii/S2211124720308093