Purposes The aim of this study was to elucidate the potential new targets for vascular remolding with hypertension.
Methods and Results In this study, we established the ouabain-induced hypertensive SD rats (OHR), the blood pressure were observed during the process, the vessel hypertrophy were detected, and the level of ET-1, NO were tested and the expression of VEGF, TGF-β1, PCNA, PKC, NOS in vessel tissue were observed during the development of remolding. Furthermore, we analysed the protein expression profiles of aortic smooth muscle in OHR of various degrees during the development of vascular remolding in hypertension, as well as in matched no treated SD rats, using a proteomic analysis of relative and absolute quantification (iTRAQ). The expressions of 33 proteins were altered 1.5-folds in OHR compared with no-treated rats. Of these proteins, Non-muscle caldesmon (CDM), Citrate synthase, Alpha-S1-casein, Alpha-S1-casein, Destrin (Actin-depolymerising factor) (ADF) and Insulin-like growth factor-binding protein 7 (IGFBP-7) were upregulated in SHR compared with contrast rats. On the other hand, the expression of Tyrosyl-DNA phosphodiesterase 1, Annexin A1, Ras-related protein Rab-8A and ATP synthase subunit e in OHR. The results from a PCR analysis revealed that the expression of the above protein meet the results respectively. The level of IGFBP-7 was more in remolding aortic strips from OHR than from rats without remolding. There are linkage between the expression of IGFBP-7 and vascular function and hypertrophy. Moreover, silence the expression IGFBP-7 treatment with siRNA technology inhibited aortic smooth muscle contraction induced by ouabain, while over-expression of IGFBP-7 promote the vascular hypertrophy. Interesting, the expression of IGFBP-7 lead to the change of level of ET-1, NO, and the change of VEGF, TGF-β1 in vessel hypertrophy, so as to support the result obtained from the proteomic analysis.
Conclusion These results suggest that the IGFBP-7 is involved in vascular remolding in ouabian-induced hypertensive rats and it may be the key target protein of ouabain on vascular remolding.
- Insulin-like growth factor-binding protein 7
- vascular remolding
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