Non-Coding RNAs in Obesity-Driven Vascular Dysfunction: Mechanisms, EndMT, and Translational Opportunities.

Area of Science:

• Vascular Biology
• Molecular Medicine
• Obesity Research

Background:

• Obesity causes systemic vascular disease via metabolic excess and adipose dysfunction.
• This leads to endothelial injury, oxidative stress, and endothelial-to-mesenchymal transition (EndMT).
• Non-coding RNAs (ncRNAs) are key regulators in the vascular wall and via extracellular vesicles (EVs).

Purpose of the Study:

• To review the role of ncRNAs in obesity-associated vascular disease.
• To explore how ncRNAs integrate signaling pathways and endothelial metabolism.
• To discuss ncRNAs as biomarkers and therapeutic targets for vascular complications of obesity.

Main Methods:

• Synthesis of evidence from single-cell, lineage-tracing, and in vitro studies.
• Analysis of circulating and EV-associated ncRNAs in obesity.
• Review of current and emerging therapeutic strategies targeting ncRNAs.

Main Results:

• ncRNAs integrate key signaling pathways (TGF-β/Smad, NF-κB, HIF-1α, Wnt/β-catenin) with endothelial metabolism and EndMT.
• Obesity triggers shifts in ncRNA networks, promoting mesenchymal phenotypes.
• Circulating ncRNAs reflect obesity status and endothelial dysfunction, improving with weight loss.

Conclusions:

• Obesity-induced vascular disease is an ncRNA-driven network disorder.
• ncRNAs are promising dynamic biomarkers for patient stratification.
• Targeting ncRNAs offers potential for novel, endothelium-specific therapeutic interventions.