ELABELA Protects Against Thoracic Aortic Dissection by Maintaining Vascular Smooth Muscle Cells Homeostasis and...

Area of Science:

• Cardiovascular Biology
• Vascular Medicine
• Aortic Diseases

Background:

• Thoracic aortic dissection (TAD) is a life-threatening condition lacking effective medical treatments.
• Disruption of vascular smooth muscle cell (VSMC) homeostasis is a key factor in TAD development.
• The role of ELABELA (ELA), a ligand for APJ, in TAD remains unclear.

Purpose of the Study:

• To investigate the effects of ELA on the development and progression of TAD.
• To elucidate the molecular mechanisms underlying ELA's action in TAD.
• To assess ELA's potential as a therapeutic target for TAD.

Main Methods:

• TAD models were induced in mice using β-aminopropionitrile monofumarate with or without Ang II.
• ELA or saline was administered to mice via osmotic minipumps.
• Transcriptomic analysis and VSMC-conditioned medium were employed to study molecular pathways.

Main Results:

• ELA infusion attenuated TAD progression and prevented aortic medial degradation, effects reversed by an APJ antagonist.
• Exogenous ELA protected VSMCs from homeostasis disruption.
• ELA inhibited the NLRP3/IL-1β pathway and modulated neutrophil extracellular trap (NET) formation.
• ELA levels were decreased in human TAD patients, with lower levels associated with higher TAD risk.

Conclusions:

• ELA plays a protective role against TAD by maintaining VSMC homeostasis, potentially via inhibiting NETosis and NLRP3/IL-1β signaling.
• ELA demonstrates potential as a pharmacological target for TAD treatment and diagnosis.