Activated protein C restores hepatic microcirculation during sepsis by modulating vasoregulator expression

Area of Science:

• Biochemistry
• Pharmacology
• Pathophysiology

Background:

• Activated protein C (aPC) has anti-coagulant, anti-inflammatory, and pro-fibrinolytic properties.
• aPC levels are reduced in sepsis patients, making aPC a potential therapeutic agent.
• Understanding aPC's mechanism in sepsis is crucial for optimizing treatment.

Purpose of the Study:

• To investigate the impact of aPC on hepatic vasoactive gene and protein expression in a sepsis model.
• To assess how aPC affects hepatic vascular responsiveness and microcirculation during sepsis.

Main Methods:

• Rats underwent cecal ligation and puncture (sepsis model) or sham surgery.
• aPC treatment was administered intravenously.
• Hepatic endothelin 1 (ET-1) and ET A receptor expression were measured.
• Intravital microscopy assessed ET-1-induced changes in liver microcirculation.

Main Results:

• aPC treatment significantly reduced hepatic ET-1 and ET A receptor mRNA and protein levels.
• aPC improved the hepatic perfusion index in septic rats without altering portal venous pressure.
• aPC enhanced red blood cell velocity, indicating hepatoprotective effects.

Conclusions:

• aPC ameliorates ET-1-mediated changes in hepatic microcirculation during sepsis.
• aPC treatment improves hepatic function and microvascular responsiveness in a septic setting.
• These findings support aPC's therapeutic potential for sepsis by improving liver perfusion and function.