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CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm
bioRxiv - Pathology Pub Date : 2020-12-30 , DOI: 10.1101/2020.12.30.424789
Eun Na Kim , Jiyoung Yu , Joon Seo Lim , Hwangkyo Jeong , Chong Jai Kim , Jae-Sung Choi , So Ra Kim , Hee-Sung Ahn , Kyunggon Kim , Se Jin Oh

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.

中文翻译:

腹主动脉瘤中的CRP免疫沉积和蛋白质组学分析

目的:对腹主动脉瘤(AAA)主动脉壁变性的分子机制了解甚少。C反应蛋白(mCRP)的单体形式沉积在受损的心血管器官中,加重了预后。然而,尚不清楚mCRP是否沉积在腹主动脉瘤(AAA)的退化主动脉中。我们调查了mCRP是否沉积在AAA中,并检查了相关的致病性信号通路。方法:分析24例AAA患者,根据血清CRP水平和mCRP沉积程度比较其组织学特征。蛋白质组学分析是在CRP免疫力强和弥漫性(n = 7)以及CRP免疫力弱,局灶性和结合性(n = 3)的AAA病例中进行的。结果:mCRP以与主动脉壁弹性层减少的病变相一致的特征模式沉积在AAA的主动脉标本中。较高的血清CRP水平与较强的mCRP免疫阳性和较大的主动脉瘤最大直径有关。AAA中的蛋白质组学分析表明,根据mCRP免疫阳性,差异表达多种蛋白质。此外,独创性途径分析表明,在具有高mCRP免疫阳性的AAA病例中,与动脉粥样硬化,急性期反应,补体系统,免疫系统和凝血相关的途径被丰富。结论:AAA显示出mCRP的特征性沉积,并且在具有强CRP免疫阳性的AAA病例中,多种潜在的病理信号通路被上调。
更新日期:2020-12-31
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