High intraluminal pressure promotes vascular inflammation via caveolin-1

Area of Science:

• Cardiovascular Biology
• Renal Physiology
• Mechanobiology

Background:

• Hypertension involves multiple systems, with emerging evidence pointing to vascular inflammation.
• The role of intraluminal pressure as a direct trigger for vascular inflammation is not fully understood.

Purpose of the Study:

• To investigate if high intraluminal pressure induces vascular inflammation.
• To identify the signaling pathways and mechanosensors involved in pressure-induced inflammation.

Main Methods:

• Assessed leukocyte adhesion in rat carotid arteries subjected to high intraluminal pressure.
• Monitored reactive oxygen species (ROS) production, arginase expression, and NF-κB translocation.
• Utilized caveolin-1 (Cav1)-deficient mice and endothelial cells to assess the role of caveolae.

Main Results:

• High intraluminal pressure (120 mmHg) for 1 hour increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries.
• Pressure induced a signaling cascade involving ROS, arginase, and NF-κB translocation, independent of angiotensin II.
• Cav1-deficient cells and mice showed protection against pressure-induced vascular inflammation and leukocyte adhesion.
• Cav1 deficiency reduced pressure-induced glomerular macrophage infiltration in vivo.

Conclusions:

• High intraluminal pressure is a direct stimulus for vascular inflammation.
• Caveolin-1 acts as a crucial mechanosensor mediating pressure-induced vascular and renal inflammation.
• Targeting Cav1 may offer therapeutic strategies for hypertension-related inflammatory conditions.