#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/...

#HutchinsonGilfordProgeriaSyndrome

Intriguing 🐭data showing that Progerin-induced #ERStress #UnfoledProteinResponse in Aorta is NOT EC-origin

Evidence from
1⃣Cdh5-tTA:tetop-LA G608G 🐭
2⃣Lmna G609G knockin 🐭

#LSA 2025
www.life-science-alliance.org/content/9/2/...

#Aging
#HutchinsonGilfordProgeriaSyndrome

Progressive Increase in Somatic Mutations in Progeroid Aortic Smooth Muscle Cells

LmnaG609G/G609G🐭
6~12 wk

SNV burdens (SComatic, MutationalPatterns) corr.
ROS
DNA damage
ER stress
p53

#GenomeMed 2026
link.springer.com/article/10.1...

#HutchinsonGilfordProgeriaSyndrome

Contrary to Progerin, Prelamin A transgene (Lmna L648R/L648R) does NOT promote Atherogenesis or Aortic Smooth Muscle Cell Loss in Ldlr-/- or Ldlr+/+🐭 (even till 52 wk of age)

#ATVB 2026
www.ahajournals.org/doi/10.1161/...

Removing progerin (pathogenic Lamin A variant in #HutchinsonGilfordProgeriaSyndrome) from #SmoothMuscleCell (or cardiomyocyte as well?), but not #EndothelialCell, ⏬progeroid HGPSrev🐭#Atherosclerosis

Aortic medial collagen is almost depleted in HGPSrev🐭!

#PNAS 2024
www.pnas.org/doi/10.1073/...

#HutchinsonGilfordProgeriaSyndrome

HGPS hiPSC #EndothelialCell Secretome screening->
#Angiopoietin2 autocrine (⏫#Angiogenesis #NitricOxide) & paracrine (⏬ #SmoothMuscleCell death #Senescence)

#BaseEditing Progerin⏫Angpt2 & HGPS EC behaviors
#Aging_Cell 2024
onlinelibrary.wiley.com/doi/10.1111/...

#HutchinsonGilfordProgeriaSyndrome

TAZ/YAP hyperactivation in Endothelial Cell of Lmna G609G/G609G🐭

⏫Aortic subendothelial fibrosis & endothelial stiffening
⏫Aortic insufficiency
⏫Atherosclerosis

However, EC phenotype NOT seen in EC-specific progeria🐭

@jci.org 2024
www.jci.org/articles/vie...

#HutchinsonGilfordProgeriaSyndrome

#Senescence/#Aging features of Isogenic HGPS #hiPSC-#EndothelialCell vs #SmoothMuscleCell

#Progerin <
Nuclear deformation <
#Senescence >
#DNADamage ~
#TelomereLength <
#Shelterin
#SASP
#Heterochromatin loss ~

#EHJOpen 2022
academic.oup.com/ehjopen/arti...