Targeting Procalcitonin Protects Vascular Barrier Integrity.

Area of Science:

• Vascular Biology
• Inflammation Research
• Sepsis Pathophysiology

Background:

• Capillary leakage is a critical complication in sepsis and major surgery, leading to microvascular dysfunction and poor outcomes.
• Procalcitonin is a known inflammation biomarker, but its role in vascular integrity was previously unclear.

Purpose of the Study:

• To investigate how procalcitonin induces endothelial hyperpermeability.
• To determine if targeting procalcitonin can protect vascular barrier integrity.

Main Methods:

• Prospective observational study in cardiac surgery patients correlating procalcitonin levels with clinical outcomes and microvascular function.
• In vitro and in vivo (mice) studies to characterize procalcitonin's effect on endothelial barrier and adherens junctions.
• Evaluation of dipeptidyl-peptidase 4 (DPP4) inhibition on procalcitonin activation in sepsis models and in patients on sitagliptin.

Main Results:

• Elevated postoperative procalcitonin correlated with increased fluid and vasopressor requirements and compromised microcirculation.
• Procalcitonin increased endothelial and pulmonary capillary permeability by destabilizing VE-cadherin.
• Targeting procalcitonin or DPP4 significantly reduced capillary leakage; sitagliptin use was linked to improved microcirculation and reduced postoperative support needs.

Conclusions:

• Procalcitonin actively contributes to endothelial hyperpermeability and vascular barrier dysfunction.
• Targeting procalcitonin signaling, particularly via DPP4 inhibition, offers a promising strategy to preserve vascular integrity in hyperprocalcitonemic states.
• This approach may mitigate complications associated with systemic inflammation, such as sepsis and post-surgical capillary leak.