CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm

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.

Unraveling the Complexity of Abdominal Aortic Aneurysm: Multiplexed Imaging Insights into C-Reactive Protein-Related Variations

“…This approach provided strong evidence suggesting that atherosclerosis-related AAA is indeed associated with inflammatory processes, further highlighting the significance of inflammation in the context of AAA. Importantly, we previously found that as serum CRP levels increased 10 , the degree of CRP deposition within atheroma also increased, supporting the active and critical role of CRP in the pathogenesis of aortic aneurysms.…”

“…In our previous study, we reported the deposition of CRP at the interface between the eroded aneurysmal vascular wall and atheromatous plaque, along with inflammatory cell infiltration in the atheroma of AAA, a phenomenon not typically observed in aortic dissection or the normal aorta 10 . In AAA specimens with high serum CRP levels, CRP deposition was more prominent and associated with a higher density of inflammatory cells, including CD68+ macrophages, as well as complement deposition, compared to AAA specimens with lower serum CRP levels, which had weak and focal CRP deposition at the aneurysmal wall.…”

“…Dale et al reported that elastin-derived peptides promote AAA formation by modulating M1/M2 macrophage polarization 30 . In addition, our previous study showed that AAA with intense CRP deposition was related to the poor prognosis of aortic aneurysm 10 . n line with these studies, the present study suggests that targeting M1/M2 macrophage polarization associated with CRP deposition could be a novel molecular approach to impede AAA progression.…”

“…Serum CRP levels were assessed just before surgery, and immunohistochemistry (IHC) staining was performed on the surgically resected aortic tissue using anti-CRP and anti-mCRP antibodies. The CRP IHC scoring method was conducted following the protocol established in our previous study on aortic aneurysms 10 Representative images of anti-CRP antibody IHC staining for the Low-CRP and High-CRP groups are shown in Figure S1.…”

Ruptured abdominal aortic aneurysm in a young male patient, a rare case report

“…His erythrocyte sedimentation rate was also elevated at 35 mm/h. The elevated CRP reflects the severe acute systemic inflammatory state relating to the aortic wall degeneration [13] , [14] with associated poor prognosis [15] . AAAs are commonly associated with atherosclerosis and inflammation while thoracic aortic aneurysms are mainly hereditary without significant atheroma [8] .…”