Artery Remodeling Under Axial Twist in Three Days Organ Culture

Abstract

Arteries often endure axial twist due to body movement and surgical procedures, but how arteries remodel under axial twist remains unclear. The objective of this study was to investigate early stage arterial wall remodeling under axial twist. Porcine carotid arteries were twisted axially and maintained for three days in ex vivo organ culture systems while the pressure and flow remained the same as untwisted controls. Cell proliferation, internal elastic lamina (IEL) fenestrae shape and size, endothelial cell (EC) morphology and orientation, as well as the expression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were quantified using immunohistochemistry staining and immunoblotting. Our results demonstrated that cell proliferation in both the intima and media were significantly higher in the twisted arteries compared to the controls. The cell proliferation in the intima increased from 1.33±0.21% to 7.63±1.89%, and in the media from 1.93±0.84% to 8.27±2.92% (p < 0.05). IEL fenestrae total area decreased from 26.07±2.13% to 14.74±0.61% and average size decreased from 169.03±18.85μm2 to 80.14±1.96μm2 (p < 0.01), but aspect ratio increased in the twisted group from 2.39±0.15 to 2.83±0.29 (p < 0.05). MMP-2 expression significantly increased (p < 0.05) while MMP-9 and TIMP-2 showed no significant difference in the twist group. The ECs in the twisted arteries were significantly elongated compared to the controls after three days. The angle between the major axis of the ECs and blood flow direction under twist was 7.46±2.44 degrees after 3 days organ culture, a decrease from the initial 15.58±1.29 degrees. These results demonstrate that axial twist can stimulate artery remodeling. These findings complement our understanding of arterial wall remodeling under mechanical stress resulting from pressure and flow variations.

Artificial Circulatory Model for Analysis of Human and Artificial Vessels

“…This system is at least somehow comparable to our ACM. However, effects of altered flow conditions have only been investigated in human saphenous veins after coronary artery bypass grafting [13]. Mundagi et al also reported on an ex vivo bioreactor that allowed an evaluation of cellular interactions in the carotid artery of pigs under controlled physiologic conditions [2].…”

“…Various models have recently been developed to understand vascular biology, Among those are ex vivo tissue culture systems described to evaluate vascular responses in relation to various biomechanical and biochemical factors [12,13]. So far, few efforts have been taken to exploit the potential of ex vivo vessel bioreactors towards a high-fidelity ex vivo replication of the hemodynamic factors affecting arterial wall behavior in an artificial environment.…”

Arterial wall remodeling under sustained axial twisting in rats

“…The lumen and outer diameters of the medial layer, as well as the intima-media wall thickness were measured. The wall thickness to lumen diameter ratio was then determined (Han and Ku 2001; Wang et al 2015). The collagen and elastin contents were quantified as the ratio of the area occupied by collagen and elastin fibers divided by the total area of the media, respectively, and the collagen to elastin (C/E) ratio was calculated as an index of arterial (medial wall) stiffness (Jones et al 2009; Zhang et al 2013).…”

“…After the animals were sacrificed, the left carotid arteries were harvested, cut into 5 μm frozen slides as described above and processed for BrdU staining (Wang et al 2015). Cell proliferation was quantified by the ratio of the proliferating cells to counterstained all vascular cells (Xiao et al 2014; Wang et al 2015). …”

“…Previously, we developed an ex vivo porcine carotid artery twisting model (Wang et al 2015). It was shown that arterial wall remodels under axial twisting as demonstrated by elevated cell proliferation and MMP expression, changes in EC shape and orientation, as well as internal elastic lamina (IEL) fenestrae shape in 3 days under axial twisting.…”