CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm

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.

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.…”

“…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 . Based on the serum CRP level and the intensity of CRP immunostaining in the aneurysmal tissue, we classified patients into two groups: the High-CRP group (patient n = 6, tissue core n = 12) with serum CRP levels ≥ 0.1 mg/dL and ≥ 3+ CRP IHC score, and the Low-CRP group (patient n = 3, tissue core n = 5) with serum CRP ≤ 0.1 mg/dL and ≤ 1+ CRP IHC score.…”

Defining atherosclerotic plaque biology by mass spectrometry-based omics approaches

“…86 Kim E. N. et al investigated the atherosclerotic plaque collected from the AAA patients and showed a high level of monomeric C reactive protein (mCRP), which correlates with the serum CRP levels and is shown to be associated with various signaling pathways related to complement activation, atherosclerosis, and thrombogenesis. 87 Lorentzen L. G. et al used a novel method to demonstrate the differences in the protein signatures of coronary artery lesion of STEMI and stable angina pectoris subjects. 88 A comprehensive targeted and untargeted proteomics by K. Theofilatoson et al on the core and periphery of plaques from 219 carotid endarterectomy samples revealed distinct signature proteins involved in plaque calcification and inflammation.…”

Monomeric C-Reactive Protein: Current Perspectives for Utilization and Inclusion as a Prognostic Indicator and Therapeutic Target

“…Specifically, expression of the pro-inflammatory highly biologically active but blood insoluble mCRP has been quantified from the plasma as particulate or cellular-bound protein and related to disease pathophysiology. In some disease conditions, the relative circulating expression of nCRP could reflect status change or severity matching the tissue deposition of mCRP-for example, Kim et al (28) found that aortic wall degeneration in patients with abdominal aortic aneurysm was associated with mCRP immunopositivity and associated aberrant signaling pathway activation; the extent of which could be confirmed and marked by the hsCRP expression and thus utilized as a prognostic indicator.…”