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Histopathological and proteomic analyses identify integrin-β1 as a potential mediator of phlebosclerosis in uremic patients

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Abstract

Background

Patients with uremia have an excessive mortality from cardiovascular disease (CVD). Arterial remodeling is mainly responsible for uremia-induced CVD and has been well studied, yet venous remodeling is poorly understood. Here we investigate the histopathology and proteomic profiles of venous remodeling in uremic patients.

Methods

Forearm cephalic veins were isolated from nine uremic patients during surgeries for arteriovenous fistula, and from nine healthy controls when applying surgical debridement. Hematoxylin–eosin, Masson’s trichrome, von Kossa, and immunohistochemistry (IHC) against proliferating cell nuclear antigen were stained for histopathology. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was executed to explore the proteome of the veins. The core regulatory protein was validated by western blot, IHC, and immunofluorescence.

Results

Phlebosclerosis, characterized by intimal rarefaction and medial thickening with disordered proliferation of vascular smooth muscle cells (VSMCs), was the prominent pathological manifestation of peripheral veins in uremic patients, while inflammatory cell infiltration, atherosclerosis or calcification were not obviously detected. iTRAQ analysis showed that 350 proteins were significantly changed in phlebosclerosis of uremic patients compared with healthy controls, of which integrin-β1 (ITGβ1) exhibited the strongest regulatory ability by intermolecular interaction network analysis. The enhanced ITGβ1 expression was mainly co-expressed with the disordered proliferation of VSMCs while a little with vascular endothelial cells in the forearm cephalic veins of uremic patients.

Conclusions

Phlebosclerosis is the prominent pathological manifestation in peripheral veins of uremic patients. This pathological alteration mainly attributes to the disordered proliferation of VSMCs, which is potentially mediated by ITGβ1.

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Data availability

The mass spectrometry proteomics data have been deposited to the ProteomeXchange database (proteomecentral.proteomexchange.org) via the PRIDE partner repository [39] under the dataset identifier PXD010883.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81671897) and Science and Technology Commission of Shanghai Municipality (17511110205).

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Correspondence to Dayong Hu or Ai Peng.

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This study was approved by the Ethics Committee of Shanghai Tenth People’s Hospital of Tongji University (#SHSY-IEC-3.0/15-60/01) and conformed to the Helsinki Declaration of 1975.

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Written informed consents were obtained from all recruited patients.

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Zhou, C., Li, C., Wang, Q. et al. Histopathological and proteomic analyses identify integrin-β1 as a potential mediator of phlebosclerosis in uremic patients. Clin Exp Nephrol 23, 1100–1108 (2019). https://doi.org/10.1007/s10157-019-01755-0

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