CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm.

Eun Na Kim,Joon Seo Lim,Chong Jai Kim,Hee-Sung Ahn,Se Jin Oh,Jae-Sung Choi,So Ra Kim,Jiyoung Yu,Hwangkyo Jeong,Kyunggon Kim,Rudolf Kirchmair

doi:10.1371/journal.pone.0245361

Abstract

ObjectiveThe 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.MethodsTwenty-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).ResultsmCRP 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.ConclusionsAAA 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.

Highlights

Abdominal aortic aneurysm (AAA), a permanent and progressive increase in the diameter of the aortic wall, is associated with 150,000–200,000 annual deaths worldwide [1]
Results monomeric form of C-reactive protein (mCRP) was deposited in the aortic specimens of abdominal aortic aneurysm (AAA) in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall
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

Summary

Introduction

Abdominal aortic aneurysm (AAA), a permanent and progressive increase in the diameter of the aortic wall, is associated with 150,000–200,000 annual deaths worldwide [1]. C-reactive protein (CRP) is an acute-phase protein that is rapidly produced from the liver and released into the bloodstream in response to various cellular injuries; as such, serum CRP level is widely used as a prognostic marker for cardiovascular diseases [5]. In terms of AAA, serum CRP level is considered as an independent risk factor [6], a predictor [7], and a prognostic marker [8]. CRP exists in a pentameric form (pCRP) and has an anti-inflammatory role [9]. When pCRP encounters damaged tissues, it dissociates into a monomeric form (mCRP) and is deposited in the damaged cell membrane [10]; subsequently, mCRP induces an inflammatory response by monocyte activation and reactive oxygen species formation to exacerbate tissue damage [11]

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Conclusion