Cardiovascular Disease

Ketosis prevents abdominal aortic aneurysm rupture through C–C chemokine receptor type 2 downregulation and enhanced extracellular matrix balance

Abdominal aortic aneurysms (AAAs) are a serious condition often linked to aging, with rupture leading to high mortality rates. Currently, there is no effective medical therapy to prevent AAA rupture.

The C–C chemokine receptor type 2 (CCR2) pathway plays a critical role in inflammation and extracellular matrix degradation, both of which contribute to AAA formation and rupture.

Researchers hypothesized that ketosis could modulate CCR2 and prevent the progression of AAA.

In this study, male rats underwent AAA formation and were assigned to one of three interventions: a standard diet, a ketogenic diet (KD), or exogenous ketones (EKB).

Rats receiving KD and EKB achieved a state of ketosis and demonstrated a significant reduction in AAA expansion and rupture rates. Rats that received a KD demonstrated the most notable effects.

Key findings:

•  Reduced AAA expansion: Rats on the ketogenic diet showed a 42% decrease in AAA diameter after 2 weeks compared to controls.
• Lower rupture rates: Rats on the ketogenic diet showed a 67% reduction in rupture rate.
• CCR2 downregulation: Ketosis reduced the expression of CCR2 in the aortic wall, leading to lower inflammation and extracellular matrix degradation. CCR2-knockout mice showed a similar protective effect.
• Improved matrix metalloproteinase (MMP) balance: Active MMP9, which promotes AAA formation, was reduced, while the stabilizing MMP9/TIMP1 complex increased, preserving the aortic wall structure.

These results suggest that ketosis could serve as a potential therapeutic approach for stabilizing AAAs and reducing the risk of rupture. Further clinical studies are needed to evaluate its efficacy in humans.