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/...
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/...
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...
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...
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...
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...
#HydrostaticPressure 120 mmHg 7 d➡️
⏫#Piezo1➡️ (⏫ #ERStress GPR78 CHOP➡️)
⏫ #SmoothMuscleCell Calcification (~20% level by 4 mM Pi)
#BBAMolBasisDis 2025
www.sciencedirect.com/science/arti...
#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
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...
#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...
METTL3⏫in👤stenotic #ArterioVenousFistula
SMC Mettl3 KO🐭
⏬AVF Intima
Mettl3-YTHDF1 stabilizes SLC7A11 mRNA➡️
⏬SMC contractile phenotype
⏫SMC proliferation/migration
⏬Lipid peroxidation
#ATVB 2025 @ahajournals.bsky.social
www.ahajournals.org/doi/full/10....
METTL3⏫in👤stenotic #ArterioVenousFistula
SMC Mettl3 KO🐭
⏬AVF Intima
Mettl3-YTHDF1 stabilizes SLC7A11 mRNA➡️
⏬SMC contractile phenotype
⏫SMC proliferation/migration
⏬Lipid peroxidation
#ATVB 2025 @ahajournals.bsky.social
www.ahajournals.org/doi/full/10....
DNA N6-methyladenine/6mA (NOT m6A) of BMP2 gene ⏬OCT4-dependent transcription & #SmoothMuscleCell Calcification
ALKBH1, an eraser of 6mA
⬇️in calcified radial artery of👤CKD
⏫aortic calcification in 🐭+Adenine diet
@jci.org 2021
www.jci.org/articles/vie...
DNA N6-methyladenine/6mA (NOT m6A) of BMP2 gene ⏬OCT4-dependent transcription & #SmoothMuscleCell Calcification
ALKBH1, an eraser of 6mA
⬇️in calcified radial artery of👤CKD
⏫aortic calcification in 🐭+Adenine diet
@jci.org 2021
www.jci.org/articles/vie...
#HydrostaticPressure➡️
⏫GPR146➡️
⏫SMC synthetic phenotype
⏫cAMP-CREB-Piezo1➡️⏫Syst/Diastolic Blood Pressure
Evidence from GPR146 KO
SMC-GPR146 KI & KO
AAV2-SM22a-GPR146 +SMC-Piezo1 KO🐭
#CircRes 2025 @ahajournals.bsky.social
www.ahajournals.org/doi/10.1161/...
#HydrostaticPressure➡️
⏫GPR146➡️
⏫SMC synthetic phenotype
⏫cAMP-CREB-Piezo1➡️⏫Syst/Diastolic Blood Pressure
Evidence from GPR146 KO
SMC-GPR146 KI & KO
AAV2-SM22a-GPR146 +SMC-Piezo1 KO🐭
#CircRes 2025 @ahajournals.bsky.social
www.ahajournals.org/doi/10.1161/...
circSETD2(14,15), an evolutionarily conserved circRNA, encodes a peptide (p-414aa👤 p-298aa🐭)➡️
dissociates HuR from c-Fos mRNA➡️
⏬SMC proliferation
⏫SMC contractile phenotype (via activating Myocd?🤔)
#Circ 2025
www.ahajournals.org/doi/10.1161/...
circSETD2(14,15), an evolutionarily conserved circRNA, encodes a peptide (p-414aa👤 p-298aa🐭)➡️
dissociates HuR from c-Fos mRNA➡️
⏬SMC proliferation
⏫SMC contractile phenotype (via activating Myocd?🤔)
#Circ 2025
www.ahajournals.org/doi/10.1161/...
EC TRPV4 activity⏫
🐭#AbdominalAorticAneurysm (local elastase)
via⏫EC #Apoptosis (how does this propagate to #SmoothMuscleCell loss) w/o altering #NitricOxide
#AortaEd
#EurJPharmacol 2024
www.sciencedirect.com/science/arti...
EC TRPV4 activity⏫
🐭#AbdominalAorticAneurysm (local elastase)
via⏫EC #Apoptosis (how does this propagate to #SmoothMuscleCell loss) w/o altering #NitricOxide
#AortaEd
#EurJPharmacol 2024
www.sciencedirect.com/science/arti...
Sorry no TAZ data😔
Guess this cascade may also work in Hypertensive SMC Hypertrophy & Collagen deposit?😁
#MucosalImmunol 2024
www.sciencedirect.com/science/arti...
Sorry no TAZ data😔
Guess this cascade may also work in Hypertensive SMC Hypertrophy & Collagen deposit?😁
#MucosalImmunol 2024
www.sciencedirect.com/science/arti...
Lyz2-CreERT2:Basp1 f/f or AAV8-shBasp1🐭+BAPN
👉abrogate thoracic aortic dilation
👉50~80%⏬ #AorticDissection Mortality
In vitro BASP1+ monocyte
⏫ SMC EC Apoptosis
#JAdvRes 2025
www.sciencedirect.com/science/arti...
Lyz2-CreERT2:Basp1 f/f or AAV8-shBasp1🐭+BAPN
👉abrogate thoracic aortic dilation
👉50~80%⏬ #AorticDissection Mortality
In vitro BASP1+ monocyte
⏫ SMC EC Apoptosis
#JAdvRes 2025
www.sciencedirect.com/science/arti...
⏬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...
⏬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...
Cartilage in Aorta😆
⏫cGAS-STING signals
Loss of contractile phenotype
#AorticAneurysm (but low rupture) as early as 2 wk, starting from abdominal part
Karl Swärd, Sebastian Albinsson labs JCI Insight 2023
insight.jci.org/articles/vie...
Cartilage in Aorta😆
⏫cGAS-STING signals
Loss of contractile phenotype
#AorticAneurysm (but low rupture) as early as 2 wk, starting from abdominal part
Karl Swärd, Sebastian Albinsson labs JCI Insight 2023
insight.jci.org/articles/vie...
Both features (LC3B, p62, GRP78/BiP) also⏫in👤#ThoracicAorticDissection
#ClonalExpansion of SMC in dissecting🐭aorta🤠
#ATVB 2019
www.ahajournals.org/doi/full/10....
Both features (LC3B, p62, GRP78/BiP) also⏫in👤#ThoracicAorticDissection
#ClonalExpansion of SMC in dissecting🐭aorta🤠
#ATVB 2019
www.ahajournals.org/doi/full/10....
SMC is the most robust responder😎
👉⏫IFN-α/γ signals, Tissue factor activity
👉SMC paracrine➡️
⏫EC permeability, PAI1 vWF release
@naturecomms.bsky.social 2024
www.nature.com/articles/s41...
SMC is the most robust responder😎
👉⏫IFN-α/γ signals, Tissue factor activity
👉SMC paracrine➡️
⏫EC permeability, PAI1 vWF release
@naturecomms.bsky.social 2024
www.nature.com/articles/s41...
⏫by Fibronectin-β1 integrin outside-in signal
⏫its migration velocity + modestly directionality
FN-immobilized sEV can't be uptaken by SMC🤓
Dr. Catherine Shanahan lab bioRxiv 2023
www.biorxiv.org/content/10.1...
⏫by Fibronectin-β1 integrin outside-in signal
⏫its migration velocity + modestly directionality
FN-immobilized sEV can't be uptaken by SMC🤓
Dr. Catherine Shanahan lab bioRxiv 2023
www.biorxiv.org/content/10.1...
#Atheroasclerosis #MAFLD #MedialArterialCalcification
Steatotic Liver-derived #ExtracellularVesicle
⏫atherosclerotic lesion +calcification
⏫MAFLD-associated arterial calcification
⏫Osteogenesis of #SmoothMuscleCell
#AdvSci 2024
onlinelibrary.wiley.com/doi/10.1002/...
#Atheroasclerosis #MAFLD #MedialArterialCalcification
Steatotic Liver-derived #ExtracellularVesicle
⏫atherosclerotic lesion +calcification
⏫MAFLD-associated arterial calcification
⏫Osteogenesis of #SmoothMuscleCell
#AdvSci 2024
onlinelibrary.wiley.com/doi/10.1002/...
⏫#ArterialStiffness
eNOS deficiency
⏬FMD
SMC disarray
Aortic Fibrosis
Mitochondrial elongation
⏬Mitochondrial respiration
#FrontPhysiol 2024
www.frontiersin.org/journals/phy...
⏫#ArterialStiffness
eNOS deficiency
⏬FMD
SMC disarray
Aortic Fibrosis
Mitochondrial elongation
⏬Mitochondrial respiration
#FrontPhysiol 2024
www.frontiersin.org/journals/phy...
Functional outcome?😬 And more data,pls😀
PCSK9 immunoreactivity in👤carotid artery atherosclerosis, preferred in cap/shoulder SMCs, ➕corr. with #WallShearStress
#VMJ_SVM 2024
journals.sagepub.com/doi/10.1177/...
Functional outcome?😬 And more data,pls😀
PCSK9 immunoreactivity in👤carotid artery atherosclerosis, preferred in cap/shoulder SMCs, ➕corr. with #WallShearStress
#VMJ_SVM 2024
journals.sagepub.com/doi/10.1177/...
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/...
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/...
A long list of DDXs⏫in labouring myometrium!😮(Fig 1A)
DDX21 RNAIP-seq▶️
901 mRNAs in Focal adhesion/ECM/TNFα/NFkB/TGFβ signaling
THBS1 downstream of DDX21
#JCMM 2024
onlinelibrary.wiley.com/doi/10.1111/...
A long list of DDXs⏫in labouring myometrium!😮(Fig 1A)
DDX21 RNAIP-seq▶️
901 mRNAs in Focal adhesion/ECM/TNFα/NFkB/TGFβ signaling
THBS1 downstream of DDX21
#JCMM 2024
onlinelibrary.wiley.com/doi/10.1111/...
2 segregatable Muscularization programs in SMCs?🤔
👉SM α-actin-based, ⏫by verteporfin (YAPi)
👉Calponin-based, ⏬by verteporfin
#AdvHealthcMater 2024
onlinelibrary.wiley.com/doi/10.1002/...
2 segregatable Muscularization programs in SMCs?🤔
👉SM α-actin-based, ⏫by verteporfin (YAPi)
👉Calponin-based, ⏬by verteporfin
#AdvHealthcMater 2024
onlinelibrary.wiley.com/doi/10.1002/...
Mapping the Senescence (SenMayo CellAge) in p16 reporter🐭aortic atherosclerotic lesions
scRNAseq GeoMx
🔥 #SmoothMuscleCell Fibroblast T
#Senolytic ABT-737 ⏫plaque collagen fibers ⏬necrotic core ⏬serum cytokines
#NatAging 2025
www.nature.com/articles/s43...
Mapping the Senescence (SenMayo CellAge) in p16 reporter🐭aortic atherosclerotic lesions
scRNAseq GeoMx
🔥 #SmoothMuscleCell Fibroblast T
#Senolytic ABT-737 ⏫plaque collagen fibers ⏬necrotic core ⏬serum cytokines
#NatAging 2025
www.nature.com/articles/s43...
The age-related accumulation of immature Lamin A, #Progerin or Farnesyl-Prelamin A, ⏫Stretch-induced loss of aortic #SmoothMuscleCell
Comparative analysis among
1⃣LmnaG609G/+
2⃣Zmpste24-/-
3⃣SM22a-Cre::Zmpste f/f::LmnaPLAO/PLAO🐭
#CellDeathDis 2025
www.nature.com/articles/s41...
The age-related accumulation of immature Lamin A, #Progerin or Farnesyl-Prelamin A, ⏫Stretch-induced loss of aortic #SmoothMuscleCell
Comparative analysis among
1⃣LmnaG609G/+
2⃣Zmpste24-/-
3⃣SM22a-Cre::Zmpste f/f::LmnaPLAO/PLAO🐭
#CellDeathDis 2025
www.nature.com/articles/s41...