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?🧐

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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

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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
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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

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

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

#Cohesinopathy

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

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

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

#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

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

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

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

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

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

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

#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

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

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

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

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