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/...

Inhibiting LDHA to prevent Ascending #AorticAneurysm #AorticRupture
🐭BAPN -/+ Oxamate or FX11

Protein/histone lactylation mainly in Mo/Mφ &👤 #ThroacicAorticDissection

Mo/Mφ with high lactylation gene score➡️Angptl4 signals to EC/SMC/fibroblast

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

⏬Mechanosensing & ⏫inflammation of aortic #EndothelialCell as a potential disease driver in #MarfanSyndrome 😎

A novel Marfan🐭➡️early #ThroacicAorticDissection #AorticRupture Fbn1G234D/G234D T50=5 wk

⏬pSMAD2 ↔️pERK1/2

#AortaEd
Hiromi Yanagisawa lab #CircRes 2025
www.ahajournals.org/doi/suppl/10...

#MarfanSyndrome #AorticRupture

Fbn1 G234D/G234D🐭
👉Early death by 5-wk of age◀️ #AorticRupture
👉⏬binding to LTBP1/2/4➡️⏬aortic TGFβ signal

Endothelial mechanosensing failure as an early event in Marfan Aortopathy!😎

#AortaEd
Hiromi Yanagisawa lab bioRxiv 2024
www.biorxiv.org/content/10.1...

#Hypertension #AorticDissection #AorticRupture

Myh11 R247C/R247C🐭+L-NAME
👉>1/3 mortality in 16-wk hypertension
👉Aortic root dissection/rupture WITHOUT aneurysm
👉⏬#SmoothMuscleCell-Elastin tethering
👉Hyperactive FAK

#AortaEd
#FrontCVMed 2025
www.frontiersin.org/journals/car...

SM22α+ #SmoothMuscleCell ATF3 KO🐭➡️ #AorticAneurysm #AorticRupture by AngII or #Aging

ATF3 physically sequestrates MDM2 (E3 ligase for p21)

ATF3 deficiency➡️
⏬p21 protein stability
⏫ds DNA breaks
⏫Micronuclei
⏫cGAS-STING
in SMCs

#AortaEd
Clin Transl Med 2024
onlinelibrary.wiley.com/doi/10.1002/...

Ascending Aorta Diameter, Growth rate (<0.1 mm/y) & Aortic events #AorticRupture #AorticDissection Death
in DANCAVAS I+II cohorts

14962 (95%♂️) 5.0 y f/up➡️
adverse thoracic aortic events
N=23 (~31/100,000 ps-yr)
96% aortic diameter <45 mm

#AortaEd
#JACC 2025
www.sciencedirect.com/science/arti...

Incidence & Prevalence of #ThoracicAorticAneurysms
Meta-analysis of 22 Studies

TAA
Incidence🟰5.3/100,000 person-year
Prevalence🟰0.16%

Thoracic #AorticRupture
Incidence🟰1.6/100,000 ps-yr

#AortaEd
#SeminThoracCardiovascSurg 2022
www.sciencedirect.com/science/arti...

CD34+ Aortic adventitial fibroblast progenitor

⏬in👤🐭Aortopathy

Forming an adventitial fibrotic collar➡️protect against #AorticRupture in🐭AAA

Ablating CD34+ cells or their Periostin+αSMA- progeny in🐭AAA
Thinned adventitia
⏫Mortality

#AortaEd
#AdvSci 2024
onlinelibrary.wiley.com/doi/full/10....

#SpatialTranscriptomics #Visium @10xGenomics #AbdominalAorticAneurysm

THBS1/Thrombospodin-1 KO in Myeloid cell, not #EndothelialCell, ⬇️ #AorticAneurysm but⬆️ #AorticRupture in 🐭AAA AngII+Apoe KO

Likely compromised TGFb-ECM-stabilizing SMCs & fibroblasts

bioRxiv 2024
www.biorxiv.org/content/10.1...

#SmoothMuscleCell #RNAEditing

Induced SMC Adar1 homo KO in adult🐭▶️ #AorticDissection #AorticRupture

SMC Adar1 het KO▶️ectopic calcification in🐭Atherosclerotic lesions
ISG15-hi SMC subcluster arises!

Will dsRNA sensing be next-gen anti-athero target?

bioRxiv 2024
www.biorxiv.org/content/10.1...

#Autophagy defect (Atg5 KO) & #ERStress in #SmoothMuscleCell⏫#AorticDissection #AorticRupture in🐭+Angiotensin II

Both features (LC3B, p62, GRP78/BiP) also⏫in👤#ThoracicAorticDissection

#ClonalExpansion of SMC in dissecting🐭aorta🤠
#ATVB 2019
www.ahajournals.org/doi/full/10....

#GutMicrobiota #AorticDissection

#GutMicrobiota-derived Indole-3-Aldehyde⏬BAPN-🐭#AorticDissection #AorticRupture

Direct effects of I3A on #SmoothMuscleCell phenotype

What happens to EC/immune cells?

Xinyu Weng, Junbo Ge labs #NutrientsMDPI 2023
www.mdpi.com/2072-6643/15...

An adult (6 mpf) #Zebrafish model of #AorticDissection #AorticRupture (without #AorticAneurysm)

Quadriple smad3a/3b/smad6a/6b crispant

🐟Aortic #FalseLumen for 1st time 👏👏👏

Melanin metabolism in #Aortopathy!?🤯

#AortaEd
bioRxiv 2024
www.biorxiv.org/content/10.1...

A must-read for anyone interested in BAPN-induced🐭#Aortopathy

Comprehensive info:
BAPN Dosage/Timing
🐭Strain/Age/Sex
Aortic Regionalization
#AorticDilation
#AorticDissection
#AorticRupture

#AortaEd

Hong Lu, Alan Daugherty labs @biorxiv-physio.bsky.social 2023
www.biorxiv.org/content/10.1...