Loss of contractile phenotype (⏬SMMHC SMTN ⏫S100A4 MMP2) of #SmoothMuscleCell & Elastin fiber in #AcuteAorticDissection

Type A/B? Any aneurysm?🧐

24 case (non-monogenic) vs 17 control

"aortic wall adjacent to the entry site of the dissection"

#AortaEd
#CJCOpen 2025
www.cjcopen.ca/article/S258...

#SIRT6 #VascularCalcification

Rat #HighFatDiet + VitD3 + Nicotine
▶️Aortic medial calcification & ⏬SIRT6

SIRT6 overexpression ⏬Palmitic acid-induced #SmoothMuscleCell Apoptosis & Osteogenesis

#JHyperten 2023
journals.lww.com/jhypertensio...

#Autophagy #VascularAging

SM22α+ #SmoothMuscleCell Atg7 KO🐭3.5 mo
Aorta myography with oscillatory tension 10 Hz

👉Peterson modulus⏫
pressure-dependent
systolic 80~300 mmHg
diastolic 40~260 mmHg

↔️🫀functions

Paul Fransen lab #PflügersArchiv 2020
link.springer.com/article/10.1...

Transcript signature of lineage-specific mouse proximal thoracic aortic #SmoothMuscleCell

Wnt1-Cre cardiac neural crest (inner media)-derived SMC
vs
Mef2c-Cre second heart field (outer media)-derived SMC

#AortaEd
David Dichek lab #ATVB 2025
www.ahajournals.org/doi/10.1161/...

1400W, an iNOS inhibitor, reduces #ThoracicAorticAneurysm #ThroacicAorticDissecion in BAPN mouse, in addition to previously reported Marfan mice

A possible role in #SmoothMuscleCell Mitochondrial fission/fusion

#AortaEd

#EurJPharm 2025
www.sciencedirect.com/science/arti...

#VascularCalcification

🐭aortic #SmoothMuscleCell in anchored 3D fibrin hydrogel for 14 d
👉Accumulate proteoglycan (IHC Proteomics)
👉No elastin fiber formation
👉TGFβ-responsive
👉Calcifiable, retaining similar individual sensitivity to 2D culture

www.sciencedirect.com/science/arti...

#SmoothMuscleCell #Aging Mechanobiology

24- vs 4-mo rat SkM feed artery

Aged SMC
👉RNAseq ⏬Contractile gene #FocalAdhesion
👉Faster kinetics⏫αSMA filament ⏫vinculin cluster to #CyclicStretch
👉Pressure Inert on 4 kPa matrix; Sensitive on 100 kPa

#FrontPhysiol 2025
www.frontiersin.org/journals/phy...

#VeinAging
Great saphenous vein 18~89 y/o

Normal
👉Subintimal longitudinal #SmoothMuscleCell bundle peak at middle age
👉Outer medial longitudinal SMC bundle ⬆️with Age

Varicose
👉Alternating zones of hypertrophic & atrophic SMCs
👉Excess collagen deposit

#JCM_MDPI 2025
www.mdpi.com/2077-0383/14...

Contribution of Gli1+ #AdventitialStemCell to #SmoothMuscleCell
❌Atherosclerosis
❌Wire-Injured Femoral Artery
✅Femoral Artery Anastomosis

1⃣Gli1-CreER;R26-tdT🐭
2⃣Myh11-Dre;Gli1-CreER;R26-IR1🐭
Gli1+ lineage➡️ZsG
Preexisting SMC➡️tdT

Adv Sci 2025
advanced.onlinelibrary.wiley.com/doi/10.1002/...

#HutchinsonGilfordProgeriaSyndrome

#SmoothMuscleCell Progerin transgene drives #EndMT #Atherosclerosis🐭

⏫Aortic Endothelial Cell permeability
⏫Lesional EC infiltr▶️ColIV- & TGFβ1-rich plaque😮

Paracrine of progeroid aortic SMC?😆

#CircAHA 2024
www.ahajournals.org/doi/10.1161/...

NET1/ARHGEF8 is a mechanosensitive Guanine Exchange Factor controlling vascular smooth muscle cells' contractility Cyclic stretch, generated by pulsatile blood pressure, has been identified as a pivotal regulator of vascular smooth muscle cell (VSMC) behavior and arterial wall homeostasis. Research has demonstrate...

🔬 New preprint !!! 👇
📃 shorturl.at/uTj8m
🧫 We identified NET1/ARHGEF8 as a stretch-sensitive RhoGEF in smooth muscle cells
Thanks to Mary-Adel Mrad and the team for their hard work 💪
#vascularbiology #smoothmusclecell #cyclicstretch↔️
@inserm.fr @cnrsbiologie.bsky.social

The quantitative analysis of Re-orientation of #SmoothMuscleCell #CollagenFiber in🐭#Atherosclerosis

#Calcification Annexin A2/5/6 (#MatrixVesicle markers)⬆️ only seen in zones of SMC/Collagen disorganization

Xufeng Niu & Yubo Fan labs Research 2025
spj.science.org/doi/10.34133...

Gelsolin as a selective #Pericyte marker vs #SmoothMuscleCell Fibroblast in mouse #SkeletalMuscle
Antibody R&D MAB8170 Cryosection

BulkRNAseq
(SkM PDGFRβ+SMA− pericyte vs PDGFRβ+SMA+ SMC) vs (Brain pericyte vs SMC)

#SciRep 2025
www.nature.com/articles/s41...

PRMT5 di-methylates H3R8 & H4R3▶️
⏬Myocardin-dependent #SmoothMuscleCell contractile gene transcription
⏫SMC proliferation/migration & intimal hyperplasia in injured🐭carotid artery

PRMT5 (& PRMT4) ⬆️in PDGBB-treated SMC &👤coronary #Atherosclerosis

#CardiovascRes 2023
academic.oup.com/cardiovascre...

PRMT5 methylates & stabilizes KLF4 protein▶️
⏫#SmoothMuscleCell proliferation/migration & intimal hyperplasia in injured🐭carotid artery

Evidence from #SmoothMuscleCell PRMT5 KO🐭 & Lentiviral PRMT5

PRMT5⬆️ in👤carotid stenosis & PDGF-BB-treated SMC

#CardioVascRes 2023
academic.oup.com/cardiovascre...

PRMT5 methylates NF-κB p65 to enhance trimethylamine N-oxide-NOX4-induced #SmoothMuscleCell inflammation

SM22α+ SMC PRMT5 KO🐭 + carotid wire injury + TMAO i.p.▶️
⏬p65 methylation
⏬Vascular cell VCAM1
⏬CD68 recruitment

#CellDeathDis 2022
www.nature.com/articles/s41...

#SmoothMuscleCell m6A Epitranscriptomics

METTL14 ⬆️in 🐭 #ThoracicAorticAneurysm (AngII+HFD) or erastin-treated SMC

Liproxstatin-1 or AAV-shMettl14⏬🐭TAA

METTL14-IGF2BP2 stabilizes ACSL4 mRNA➡️
SMC #Ferroptosis

SRAMP➡️m6A site prediction

#AJPCellPhys 2025
journals.physiology.org/doi/full/10....

#SmoothMuscleCell Mettl14, ⬆️in injured artery, aggravates #IntimalHyperplasia via ⏫nascent KLF4 & SERPINE1 mRNA synthesis (Not impacting mRNA stability)

Likely Mettl3, but not other m6A readers/writers/erasers, plays a minor role

@insight.jci.org 2025
insight.jci.org/articles/vie...

#SmoothMuscleCell Epitranscriptomics

METTL3-YTHDC1 (m6A reader) ⏫SGK1 mRNA synthesis (but not stability)

135 METTL3 target genes by RNAseq+MeRIPseq in rat SMC

SMC Mettl3 KO🐭➡️
⏬carotid #IntimalHyperplasia➡️
⏫by AAV9-SM22a-SGK1

#ATVB 2025 @ahascience.bsky.social
www.ahajournals.org/doi/10.1161/...

NRIP2+ #SmoothMuscleCell (likely mediating metabolic resilience by Leptin signaling) #AorticDissection

Leptin antagonist R128Q or AAV9-SM22a-NRIP2
⏬🐭AD #AorticRupture (BAPN)
⏫contractile SMC
⏫SMC mitochondrial ultrastructure & OXPHOS

#AdvSci 2025
advanced.onlinelibrary.wiley.com/doi/10.1002/...

#VascularCalcification #SmoothMuscleCell m6A Epitranscriptomics

High Pi ⏬METTL3 in SMCs

METTL3-YTHDF2 destabilizes RUNX2 mRNA & ⏬ SMC Osteogenesis

S-Adenosylhomocysteine METTL3/14i aggravates aortic calcification in CKD 🐭 (adenine + hi Pi diet)

#CommsBio 2025
www.nature.com/articles/s42...

⏫Fatty Acid Uptake & β-oxidation in Asthmatic Bronchial #SmoothMuscleCell

#Proteomics #ImagingMassSpec 👤bronchial biopsy➡️
⏫CPT2
⏬Arachidonate Stearate Linoleate
in bronchial SMC Not Epithelium

CPT1i, CPT2i, LDLR Ab ⏬bronchial SMC prolifer & OXPHOS

#ERJ 2021
publications.ersnet.org/content/erj/...

GPR153-cAMP/CREB-#YAP/TAZ or -NFκB cascades in #EndothelialCell #SmoothMuscleCell

GPR153
⏫in SMC in intima, atheroma, MI ischemic zone
⏫in EC in inflamed SkM, Brain

Myh11+ SMC Gpr153 KO 🐭
Injured artery

Slco1c1+ brain EC Gpr153 KO 🐭
EAE & Stroke

#NatComm 2025
www.nature.com/articles/s41...

#SmoothMuscleCell m6A Epitranscriptomics

METTL3 as a direct target gene of YY1

METTL3-IGF2BP1 stabilizes MYH11 MYLK2 TGFβ2 mRNAs

SMC Yy1 or Mettl3 KO🐭
⏬vasoconstriction
↔️vasorelaxation

AAV-SM22-METTL2 iv ⏫arterial contractility of SMC Yy1 KO🐭

#CardiovascRes 2025
academic.oup.com/cardiovascre...

#SmoothMuscleCell m6A Epitranscriptomics

METTL3-YTHDF3 ⏫Profilin-1 mRNA translation➡️
⏫SMC proliferation migration
⏬SMC contractile phenotype

METTL3 YTHDF3 PFN1 ⬆️in SMC+PDGFBB & injured carotid artery

SMC Mettl3 or Pfn1 KO🐭➡️
⏬carotid Neointima

#ATVB 2024
www.ahajournals.org/doi/10.1161/...

BRD4 stabilizes NIPBL (cohesion loading) on chromatin & maintains chromatin loops & genome folding

Wnt1+ Neural Crest Brd4 KO🐭
👉⏬ #SmoothMuscleCell on aortic arch e11.5, aorta & pulmonary artery e14.5
👉Craniofacial defects
👉100% perinatal lethality

#NatGenet 2021
www.nature.com/articles/s41...

#VascularCalcification Mechanobiology

#HydrostaticPressure 120 mmHg 7 d➡️
⏫#Piezo1➡️ (⏫ #ERStress GPR78 CHOP➡️)
⏫ #SmoothMuscleCell Calcification (~20% level by 4 mM Pi)

#BBAMolBasisDis 2025
www.sciencedirect.com/science/arti...

#SmoothMuscleCell DOT1L, H3K79 methyltransferase, KO🐭
⏬lesion burden, Mφ
⏫plaque stability

DOT1L ⬆️in SMC+PDGFBB, 👤carotid #Atherosclerosis, 👤popliteal arterial aneursym

shDOT1L in SMC➡️
⏫contractile phenotype

75% 1-h PDGFBB-activated genes are H3K79me2+

#EHJ 2022
academic.oup.com/eurheartj/ar...

Histone Variants
#SmoothMuscleCell

1⃣H2A.Z
⬇️in #Atherosclerosis
⏫SMC contractile gene
#CircAHA 2018
www.ahajournals.org/doi/10.1161/...
#BMCGenom 2025
bmcgenomics.biomedcentral.com/articles/10....

2⃣H3.3B
⬆️in #AorticDissection
⏫SMC synthetic genes
#Genomics 2023
www.sciencedirect.com/science/arti...

#Atherosclerosis Epitranscriptomics

Cell type-specific dysregulation of m6A machinery in atherogenic phenotypes
#EndothelialCell ALKBH5
#SmoothMuscleCell WTAP
Mφ METTL3 YTHDF2

Re-analysis of scRNAseq Wirka's Nat Med 2019
pmc.ncbi.nlm.nih.gov/articles/PMC...

#THNO 2025
www.thno.org/v15p4785.htm