Ketosis Prevents Abdominal Aortic Aneurysm Rupture Through CCR2 Downregulation and Enhanced MMP Balance

Area of Science:

• Vascular Biology
• Metabolic Disease
• Inflammation Research

Background:

• Abdominal aortic aneurysms (AAAs) are a significant health concern, particularly in aging populations, with rupture leading to high mortality.
• Current medical therapies for AAAs lack preventative efficacy, highlighting the need for novel treatment strategies.
• The monocyte chemoattractant protein (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis is crucial in AAA pathogenesis, regulating inflammation and extracellular matrix stability.

Approach:

• This study investigated the therapeutic potential of systemic ketosis in mitigating AAA progression and rupture.
• Male Sprague-Dawley rats underwent surgical AAA induction and received either a standard diet, ketogenic diet (KD), or exogenous ketone body (EKB) supplements.
• AAA progression, rupture incidence, inflammatory markers, and extracellular matrix integrity were assessed in animals subjected to different dietary interventions.

Key Points:

• Animals in a state of ketosis (achieved via KD or EKB) exhibited significantly reduced AAA expansion and a lower incidence of rupture.
• Ketosis led to decreased CCR2 expression, reduced inflammatory cytokine levels, and fewer infiltrating macrophages within AAA tissues.
• Aortic wall analysis revealed that ketosis improved the balance of matrix-metalloproteinases (MMPs), reduced extracellular matrix degradation, and increased collagen content.

Conclusions:

• Systemic ketosis demonstrates a significant therapeutic role in managing abdominal aortic aneurysm pathobiology.
• Modulating the CCR2 axis and reducing vascular inflammation are key mechanisms through which ketosis exerts its protective effects.
• These findings support further research into ketosis as a potential preventative and therapeutic strategy for individuals at risk of or diagnosed with AAAs.