Change in high-sensitive C-reactive protein during abdominal aortic aneurysm formation

Area of Science:

• Cardiovascular Biology
• Inflammation Research
• Vascular Medicine

Background:

• Abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by aortic dilation.
• The role of inflammation, particularly C-reactive protein (CRP), in AAA pathogenesis is not fully understood.
• High-sensitive C-reactive protein (hsCRP) is a known marker of systemic inflammation.

Purpose of the Study:

• To elucidate the relationship between high-sensitive C-reactive protein (hsCRP) release and abdominal aortic aneurysm (AAA) formation.
• To investigate the source and mechanism of hsCRP production in AAA.

Main Methods:

• Established a rabbit model of AAA using elastase perfusion.
• Quantified serum hsCRP levels using ELISA at various time points.
• Utilized immunostaining, Western blot, and RT-PCR to determine the source of CRP.
• Examined hsCRP production in isolated aortic ring explants.
• Investigated the role of stretch-activated channels and nuclear factor-kappaB (NF-κB) signaling.

Main Results:

• Serum hsCRP levels significantly increased (>200%) in the AAA model compared to controls, starting by day 5 and correlating with vessel dilation.
• In early stages, increased CRP originated from the liver; in later stages, it derived from the dilated aorta itself.
• Isolated aortic rings from AAA rabbits showed increased hsCRP production.
• Inhibition of stretch-activated channels and NF-κB activation blocked hsCRP production in aortic rings.

Conclusions:

• Increased serum hsCRP in AAA formation originates from the aneurysmal artery wall, particularly with degenerating elastic lamina.
• Mechanical stretch through stretch-activated channels triggers NF-κB translocation, leading to hsCRP production in AAA.
• hsCRP is a key inflammatory mediator directly involved in AAA pathogenesis.