Endothelial Dysfunction in the Context of Blood-Brain Barrier Modeling.

Area of Science:

• Cardiovascular Biology
• Cellular Pathophysiology

Background:

• Endothelial dysfunction is a key factor in cardiovascular diseases like hypertension and microangiopathy.
• Current definitions focus on reduced vasodilation, increased permeability, and inflammation.
• Existing in vitro models lack physiological relevance for studying endothelial dysfunction.

Purpose of the Study:

• To propose expanded criteria for defining endothelial dysfunction.
• To introduce novel in vitro models that better mimic physiological conditions.
• To identify reliable biomarkers for endothelial dysfunction.

Main Methods:

• Review and propose pathophysiological criteria for endothelial dysfunction.
• Utilize in vitro models with pulsatile flow and specific coatings.
• Employ conditioned media to simulate paracrine effects.
• Analyze gene and protein expression from endothelial cell lysates.

Main Results:

• Proposed extending endothelial dysfunction criteria to include altered mechanotransduction and endothelial-to-mesenchymal transition.
• Identified limitations of current biomarkers (IL-6, IL-8, MCP-1/CCL2) for in vivo diagnostics.
• Developed flow-sensitive in vitro models with high physiological relevance.

Conclusions:

• Expanded criteria offer a more comprehensive definition of endothelial dysfunction.
• Novel in vitro models improve the study of endothelial pathophysiology, particularly for the blood-brain barrier.
• Further research is needed to validate biomarkers and refine diagnostic approaches.