Effects of #Aneuploidy on cell behavior & function
Cause:
ROS
DNA replication
mitosis
mechanical confinement
Direct dosage + secondary Effect:
Redox, bioenergetic, proteostasis, Osmosis
Cancer, Aging
Dr Rong Li & Jin Zhu Nature Reviews MCB 2023
https://www.nature.com/articles/s41580-021-00436-9
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Any evidence on #Aneuploidy in cardiovascular biology?
From Abraham Aviv lab @ATHjournal 2001
Age-dependent aneuploidy & telomere length of the human vascular endothelium
https://www.atherosclerosis-journal.com/article/S0021-9150(01)00506-8/fulltext
Tetrasomy Chr6 Chr16
Loss ChrY
Aneuploidy in cardiovascular diseases?🧐
====
Mice with #SpindleAssemblyCheckpoint protein BubR1 deficiency have a spectrum of vascular defects
Vascular BubR1 1/3
Aging-Associated Vascular Phenotype in Mutant Mice With Low Levels of BubR1
Dr. Jan van Deursen lab @StrokeAHA_ASA 2007
https://www.ahajournals.org/doi/10.1161/01.STR.0000257967.86132.01
=======
Vascular BubR1 2/3
BubR1 Insufficiency Inhibits #NeointimalHyperplasia Through Impaired Vascular #SmoothMuscleCell Proliferation in Mice
Dr. Takuya Matsumoto lab @atvbahajournals 2014
https://www.ahajournals.org/doi/10.1161/ATVBAHA.114.304737
====
Vascular BubR1 3/3
BubR1 insufficiency impairs #Angiogenesis in aging and in experimental critical limb ischemic mice
Dr. Takuya Matsumoto lab @JVascSurg 2018
https://www.jvascsurg.org/article/S0741-5214(17)32041-4/fulltext
#NeointimalHyperplasia #aneuploidy #SpindleAssemblyCheckpoint #SmoothMuscleCell #angiogenesis
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
#Aortopathy #fibrosis #emphysema #EndothelialCell #marfansyndrome #SmoothMuscleCell
Epigenetics #PulmonaryArterialHypertension
JMJD1C a histone demethylase
⏫p-STAT3->
⏫#Glycolysis HK2/PGK1/LDHA->
⏫PA #SmoothMuscleCell Proliferation
Serum Lactate⏬by AAV2-shJMJD1C in🐭#Hypoxia-PAH
Local effect on #EndMT?
Dr H Zhao lab Cell Death Discovery 2023
https://www.nature.com/articles/s41420-023-01390-5
#SmoothMuscleCell #hypoxia #EndMT #PulmonaryArterialHypertension #glycolysis
BRD4 (acetyl lysine reader)-NIPBL (cohesin loading ) complex is critical to #NeuralCrest differentiation into #SmoothMuscleCell
BRD4 depletion->⏬#GenomeFolding+loop extrusion
BRD4 in #AorticAneurysm?
Dr. Rajan Jain lab Nature Genet 2021
https://www.nature.com/articles/s41588-021-00934-8
#neuralcrest #SmoothMuscleCell #aorticaneurysm #Cohesinopathy #GenomeFolding
Striking Pulmomary #Vasculitis in #COVID19
3 case+2 Ctrl
Thickened+Broken elastin in hyalinizing arterial wall😎
Thbs1-hi CD163+ non-canonical Monocyte in fatal COVID! To activate platelet only?🧐
Dr. Kiyoshi Hirahara & Toshinori Nakayama labs PNAS 2022
https://www.pnas.org/doi/10.1073/pnas.2203437119
Plasma MYL9 level corr. with COVID severity!
And look at these crazy MYL9/12+ thrombi in small pulmonary arteries😬
What's the role of MYL9, a #SmoothMuscleCell contractile protein, in platelets?
This leads me into another wonderland (🐰hole)
Platelet-deposited MYL9/12 as Luminal scaffold guiding T-cell migration!?😈
Dr. Toshinori Nakayama lab Sci Immunology 2016
https://www.science.org/doi/10.1126/sciimmunol.aaf9154
Another intriguing paper on leukocyte vs arterial mural cell-derived MYL9/12 & #Vasculitis 😆
Increased Myosin light chain 9 expression during #KawasakiDisease Vasculitis
Dr. Motoko Kimura & Hiromichi Hamada labs Front Immunol 2022
https://www.frontiersin.org/articles/10.3389/fimmu.2022.1036672/full
#vasculitis #KawasakiDisease #COVID19 #SmoothMuscleCell
De Novo pathogenic variant of miR-145-5p (het?😃) in #MultisystemSmoothMuscleDysfunctionSyndrome #RareDisease
+mRNA & miR transcriptomes of patient skin fibroblast-/+TGFβ1 😋
Dr Mark Lindsay lab JCI 2023
@MarkELindsay
@markelindsay
https://www.jci.org/articles/view/166497
miR-145-5p is a master miRNA to maintain #SmoothMuscleCell contractile phenotype
My favorite among the earliest miR-145 papers👇
Acquisition of the contractile phenotype by murine arterial SMCs depends on the Mir143/145 gene cluster
JCI 2009
https://www.jci.org/articles/view/38864
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miR-145
CARMN
SMILR
...
The (re-)arising of smooth muscle-enriched non-coding RNAs makes me really nostalgic for my PhD days & nights😸 in Calgary
#MultisystemSmoothMuscleDysfunctionSyndrome #raredisease #SmoothMuscleCell
#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
#ThoracicAorticAneurysm #SmoothMuscleCell #EndothelialCell
Arterial dissections: Common features and new perspectives
A comprehensive review covering diverse arterial beds
Biomechanics
#EndothelialCell+#SmoothMuscleCell plasticity
Genetics
TGFβ, ECM
Dr. Robert Graham lab Frontiers Cardiovascular Medicine 2022
https://www.frontiersin.org/articles/10.3389/fcvm.2022.1055862/full
#EndothelialCell #SmoothMuscleCell
Spatial Atlas of human Lung
Spatially-resolved multi-omics-> #AirwaySubmucosalGland-associated Lymphoid niche for IgA #PlasmaCell + T cells via CCL28/IL6/APRIL paracrine
5 locations, 13 patients
Systemic vs Pulmonary vascular trees
Immune recruiting venous NG2-ABCC9+ICAM1+ #Pericyte is abundant in CCL2/19/21 & CXCL12🤠
Love to dig into transcriptomes of systemic vs pulmonary #SmoothMuscleCell & pericytes along the bronchial tree😋
A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
Love this powerful molecular micro-anatomy for human Lung👍
A great starting point for my Holiday-specific continued biomedical education on Lung🎄
Dr. Sarah Teichmann & Kerstin Meyer lab Nature Genetics 2022
https://www.nature.com/articles/s41588-022-01243-4
#AirwaySubmucosalGland #PlasmaCell #Pericyte #SmoothMuscleCell
An autosomal (Chr2) Myh11-CreERT2🐭model to enable #SmoothMuscleCell-specific KO & lineage tracing in Both MALE & FEMALE!👍
Previous mouse Myh11-Cre transgenes are Y-linked
Dr. Gary Owens lab ATVB 2022
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318160
IL-1β & Macrophage-like #SmoothMuscleCell/SMC-derived #FoamCell
scRNAseq👤calcified #Atherosclerosis (proximal vs core)->
Ligand-SMC receptor map + Mɸ-like SMC transcription network->
⏫IL1β-⏬STAT3
AAV9-Cas9-sgIL1β for🐭
Dr. Suxin Luo lab Comms Bio 2022
https://www.nature.com/articles/s42003-022-04255-2
#FoamCell #atherosclerosis #SmoothMuscleCell
ApoE KO🐶♂️normal diet 18 mo
Multi-arterial #Atherosclerosis->
MI/Stroke/Gangrene
scRNAseq athero-prone vs -resistant arteries
#TenascinC+ #SmoothMuscleCell - LTBP1+ myofibroblast transition in atherogenesis
Dr. X. Wang, YB Zhang, X Ji labs Aging Dis 2022
http://www.aginganddisease.org/EN/10.14336/AD.2022.0313
#TenascinC #atherosclerosis #SmoothMuscleCell
SM22+ #SmoothMuscleCell LRP1 KO->
Spontaneous #SuperiorMesentericArtery Aneurysm
Baseline+Injured carotid arterial defect
(Intensive neointimal Elastin deposits!😈)
⏫Angiotensin+TGFβ signals
Dr. Alan Daugherty & Dudley Strickland labs @JCI_insight 2022
https://insight.jci.org/articles/view/164751
There is a long research history on LRP1 with SMC & arterial wall integrity, starting with this👇
LRP: Role in Vascular Wall Integrity and Protection from Atherosclerosis
Dr. Joachim Herz lab Science 2003
https://www.science.org/doi/10.1126/science.1082095
#SmoothMuscleCell #SuperiorMesentericArtery
Vascular #SmoothMuscleCell dysfunction in #Neurodegeneration
Vasculo-neuronal-inflammatory triad
Hypercontractile VSMC
⏬Clearance receptors for Aβ
Autoimmune-related SMC degeneration in #AlzheimersDisease
Dr. Genevieve Hayes lab @FrontNeurosci 2022
https://www.frontiersin.org/articles/10.3389/fnins.2022.1010164/full
#Neurodegeneration #alzheimersdisease #SmoothMuscleCell
#SmoothMuscleCell Piezo1 promotes high Phosphate-induced #Calcification & osteogenic differentiation of cultured👤aortic SMC (& culture🐭aorta)
How Piezo1-Ca2+ elevates expression of Runx2 & Transglutaminase 2?
Dr. Beatrix Dienes lab Front Physiol 2022
https://www.frontiersin.org/articles/10.3389/fphys.2022.1037230/full
#calcification #SmoothMuscleCell
An impressive panorama of Trimethylamine N-oxide/TMAO on👤aortic #EndothelialCell
⏫Traits of #TrainedImmunity/Inflammation
Metabolic reprogramming
Kinome & transcriptional network
Intriguing role of PERK & mitoROS
In addition to Liver, Aorta (#SmoothMuscleCell/#Pericyte/Fibroblast/Mɸ?) may🤔 also oxidize #GutMicrobiota-derived trimethylamine/TMA into Trimethylamine N-oxide/TMAO
What is the local/Aortic vs circulating TMAO level?🧐
Wait for🐭tissue-specific KO of FMO3 (Oxidizing TMA)😆
Dr. Xiaofeng Yang lab JCI insight 2022
https://insight.jci.org/articles/view/158183
#EndothelialCell #TrainedImmunity #SmoothMuscleCell #gutmicrobiota
Itga8-CreERT2, a novel tamoxifen-inducible #SmoothMuscleCell-specific Cre🐭
Selective for Vascular over Visceral (GI/Airway...) SMC🤠
Critical comparison (+Aorta transcriptomes) vs Myh11-CreERT2
Dr. Qing Lyu & Joseph Miano labs Nature Cardiovascular Research 2022
https://www.nature.com/articles/s44161-022-00162-1
Chromatin landscape dynamics of #SmoothMuscleCell in #Atherosclerosis🐭
Integrated scATACseq+scRNAseq+lineage tracing analysis reveals a protective role of ATF3 in atherogenic #Complement 3+ SMC
Dr. Ying Wang & Nicholas Leeper lab #CardiovascRes 2022
https://academic.oup.com/cardiovascres/article/118/13/2792/6438000
#atherosclerosis #complement #CardiovascRes #SmoothMuscleCell
Airway #SmoothMuscleCell forms Collagen III microniche⏫🫁#Metastasis of #BladderCancer
via DDR1-HSP90-Stat3 axis
In primary #MuscleInvasiveBladderCarcinoma Collagen I-DDR1 axis⏫tumor invasiveness
Dr. Keith Syson Chan lab Nature Comms 2019
https://www.nature.com/articles/s41467-019-09878-4
#SmoothMuscleCell #metastasis #MuscleInvasiveBladderCarcinoma #bladdercancer
Airway #SmoothMuscleCell #Asthma Inflammation
SMMHC-driven #Integrin α7 transgene in ovalbumin♀️🐭->
⏬Airway leukocyte infiltration
⏬Pulmonary resistance (not compliance)
Re-balanced cytokine/chemokine production
Dr. Mariam Ba lab FASEB Bioadv 2022
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fba.2022-00050
#integrin #SmoothMuscleCell #asthma