ES 2024 Exploring bradykinin: A common mediator in the pathophysiology of sepsis and atherosclerotic cardiovascular disease

Siti Zubaidah Mohd Zahari

Mohd Zahari Siti-Zubaidah, Harman-Shah Harafinova, Abdullahi Nuradeen Liba, Muhammad Luqman Nordin, Kamarul Ariffin Hambali, Hawa Nordin Siti.

Vascular Pharmacology. Sept 2024;156:107414

Background

This article explores a chemical in our body called bradykinin, which plays a role in two major health problems: sepsis (a life-threatening reaction to infection) and atherosclerotic cardiovascular disease (ASCVD) (a condition where arteries get clogged, leading to heart attacks or strokes).

Though these diseases seem very different, the article shows they have some common triggers — especially inflammation, blood clotting, and problems with a hormone system called the renin-angiotensin system (RAS). Bradykinin is involved in all three.

Key Findings:

Inflammation

• Sepsis involves intense inflammation due to infection.
• ASCVD involves long-term, low-level inflammation caused by things like high cholesterol or diabetes.
• Bradykinin can trigger or worsen inflammation in both conditions.

Blood Clotting (Thrombosis)

• In sepsis, clots form as the body tries to trap bacteria.
• In ASCVD, clots form on artery plaques and can cause heart attacks or strokes.
• Bradykinin may reduce some harmful clotting, especially in sepsis.

RAS System

• This system helps control blood pressure and fluid balance.
• It goes haywire in both sepsis and ASCVD.
• Bradykinin interacts with this system and might help balance it — though the effects are still being studied.

Use in Treatments and Monitoring

• Bradykinin or its precursor (kininogen) could be used to track disease severity, especially in sepsis.
• Blocking bradykinin receptors has shown mixed results in both animal and human studies.
• Some treatments, like ACE inhibitors or recombinant ACE2, may work better because they affect both the RAS and bradykinin systems.

Conclusion

Bradykinin plays a double-edged role in sepsis and heart disease. It might help fight infection and prevent clots, but too much of it can cause low blood pressure and worsen inflammation.

Currently, there’s no perfect way to control or use bradykinin in treatment — but it may be useful to monitor how sick someone is, especially in sepsis. There’s also potential for new drugs targeting bradykinin to improve care, but more studies are needed before they’re ready for regular use.