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Updated: Apr 14, 2026

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Integrating Inflammatory, Hemodynamic, and Metabolic Cues: Context-Dependent and Mechanosensitive Regulation of

Genesis Aaliyah Campbell1,2, Omaida Caridad Velazquez1,2,3, Zhao-Jun Liu1,2

  • 1DeWitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Cells
|April 13, 2026
PubMed

Insights

Endothelial dysfunction in cardiovascular disease (CVD) involves the Notch signaling pathway. Understanding its complex regulation is key to developing targeted therapies for CVD.

Area of Science:

  • Cardiovascular Biology
  • Molecular Signaling
  • Vascular Microenvironment

Background:

  • Endothelial dysfunction is central to cardiovascular disease (CVD), involving complex environmental cue integration.
  • The endothelial Notch signaling pathway is crucial but its role in adult CVD is not fully understood.
  • Both excessive and insufficient Notch activation are linked to cardiovascular pathology.

Purpose of the Study:

  • To review the mechanistic regulation of endothelial Notch signaling.
  • To contextualize Notch pathway dysregulation in major CVD phenotypes.
  • To highlight the need for precision therapies targeting Notch signaling in CVD.

Main Methods:

  • Literature review synthesizing current evidence on endothelial Notch signaling.
  • Analysis of Notch pathway's integration of hemodynamic, metabolic, and inflammatory cues.
  • Contextualization of dysregulation across various CVD phenotypes.

Main Results:

  • Endothelial Notch signaling is context-dependent and integrates multiple cues.
  • Dysregulation of Notch signaling contributes to cardiovascular pathology.
  • Current understanding is insufficient to guide precise therapeutic strategies.

Conclusions:

  • Further research is needed to elucidate the precise mechanisms of endothelial Notch signaling in CVD.
  • Precision-based therapeutic strategies are required to restore physiological Notch signaling.
  • Targeting Notch signaling offers potential for novel CVD treatments without global pathway suppression.

Keywords:
cardiovascular diseasecontext-dependent signalingendothelial Notch signalingendothelial dysfunctioninflammationligand biasmechanosensitive signalingmetabolic stressshear stressvascular remodeling

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