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Histopathological and proteomic analyses identify integrin-β1 as a potential mediator of phlebosclerosis in uremic
Chunyu Zhou1, Changbin Li1, Qiang Wang2
1Center for Nephrology and Metabolomics and Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Insights
Uremic patients develop phlebosclerosis, a venous remodeling characterized by smooth muscle cell proliferation potentially mediated by integrin-β1 (ITGβ1). This study reveals key insights into venous pathology in uremia.
Area of Science:
- Vascular Biology
- Nephrology
- Proteomics
Background:
- Cardiovascular disease (CVD) mortality is high in uremic patients.
- While arterial remodeling is studied, venous remodeling in uremia is poorly understood.
- This study investigates venous remodeling in uremic patients.
Purpose of the Study:
- To investigate the histopathology of venous remodeling in uremic patients.
- To explore the proteomic profiles of veins from uremic patients.
- To identify key proteins involved in uremia-induced venous remodeling.
Main Methods:
- Forearm cephalic veins were obtained from uremic patients and healthy controls.
- Histopathological analysis included H&E, Masson's trichrome, von Kossa, and IHC for PCNA.
- Proteomic analysis was performed using iTRAQ, with key proteins validated by Western blot, IHC, and immunofluorescence.
Main Results:
- Phlebosclerosis, marked by intimal rarefaction and medial thickening with disordered VSMC proliferation, was observed in uremic veins.
- iTRAQ identified 350 significantly changed proteins, with integrin-β1 (ITGβ1) showing the strongest regulatory potential.
- Enhanced ITGβ1 expression correlated with VSMC proliferation in uremic veins.
Conclusions:
- Phlebosclerosis is the primary pathological finding in peripheral veins of uremic patients.
- Disordered VSMC proliferation drives this pathological alteration.
- Integrin-β1 (ITGβ1) is a potential mediator of uremia-induced venous remodeling.
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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