Abstract
Objective The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways.
Methods Twenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n=7) and those with weak, focal, and junctional CRP immunopositivity (n=3).
Results mCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity.
Conclusions AAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.
Abbreviations
- AAA
- abdominal aortic aneurysm
- AAA-high mCRP
- abdominal aortic aneurysm with strong and diffuse mCRP immunopositivity
- AAA-low mCRP
- abdominal aortic aneurysm with weak, focal and junctional mCRP immunopositivity
- AAD
- ascending aortic dissection
- CRP
- C-reactive protein
- DEPs
- differentially expressed proteins
- FDR
- false discovery rate
- FFPE
- formalin-fixed paraffin-embedded
- FKBP2
- FK506-binding protein 2
- H&E
- hematoxylin and eosin
- hsCRP
- high sensitive C-reactive protein
- IPA
- ingenuity pathway analysis
- IRB
- institutional review board
- LC-MS/MS
- liquid chromatography with tandem mass spectrometry
- LXR/RXR
- liver X receptor/retinoid X receptor
- MCP-1
- monocyte chemoattractant protein-1
- mCRP
- monomeric form of C-reactive protein
- MMPs
- matrix metalloproteinases
- PCA
- principal component analysis
- pCRP
- pentameric form of C-reactive protein
- WBC
- white blood cell count