Retracted: Transforming Growth Factor Beta‐1 Promotes Smooth Muscle Cell Proliferation and Migration in an Arteriovenous Fistulae: The Role of Wall Shear Stress

Abstract

The wall shear stress (WSS) as a mechanical stimuli to venous wall has a significant role in neointimal hyperplasia of arteriovenous fistulae (AVF), which is often related to the proliferation and migration of vascular smooth muscle cells (VSMCs). Transforming growth factor beta-1 (TGF-β1) has the function of promoting VSMCs proliferation and migration. Our study is to detect the correlation between WSS, TGF-β1, VSMCs proliferation, and neointimal hyperplasia. An "end-to-side" AVF canine model was created. We choose four typical vein regions containing arteriovenous anastomosis segment (A-V), juxta-anastomotic segment (J-V), juxta-ligation segment (L-V), and proximal vein (P-V). The expression of TGF-β1 and α-SMA of different positions was then measured and the transwell assay was used to measure the VSMC migration with different concentrations of rhTGF-β1 or for different time points in an in vitro study.Neointimal hyperplasia and higher expression of TGF-β1and α-SMA in the inner wall of sites J-V and L-V(low and disturbed WSS) was more obvious compared to the P-V, A-V sites and outer wall of L-V and J-V segment (high and laminar WSS) (P < 0.01). Transwell assay reveals that the migration of VSMCs was up-regulated following the increase of rhTGF-β1 or for a longer time. The WSS levels have a strong inverse correlation with neointimal hyperplasia. VSMCs do not only proliferate but also migrate from the media to the intima. rhTGF-β1 can stimulate migration of VSMCs in a time-dependent and dose-dependent fashion. The neointimal formation of AVF might be a local proliferative process through WSS-TGF-β1 up-regulation.

Mechanosensitive pathways are regulated by mechanosensitive miRNA clusters in endothelial cells

“…A further, focussed analysis of the signal transduction pathways revealed that 41 signalling pathways were affected by the reduction in shear stress. These included well-known shear stress-sensitive pathways such as eNOS and MAPK (Wang et al 2014;Riquelme et al 2015;Lee et al 2017;Kunnen et al 2018), recently established mechanosensitive pathways such as NOTCH and WnT (Kuo et al 2015;Kuo et al 2015;Jia et al 2018;Kunnen et al 2018;Xu et al 2018;Yang et al 2018;Bondareva et al 2019;Gater et al 2019;Han et al 2019;Kouzbari et al 2019;Varshney et al 2019;Yue et al 2019) and currently unknown mechanosensitive pathways like insulin (Table 2).…”