Artery Remodeling Under Axial Twist in Three Days Organ Culture
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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 ± 18.85 μm2 to 80.14 ± 1.96 μm2 (p < 0.01), but aspect ratio increased in the twist 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.
KeywordsTorsion Wall remodeling Matrix metalloproteinase Internal elastic lamina Endothelial cell morphology Cell proliferation Ex vivo Artery Porcine
This work was supported by National Natural Science Foundation of China through Grant 11229202 and by the National Institutes of Health through Grant R01HL095852. It was also partially supported through HHSN 268201000036C (N01-HV-00244) for the San Antonio Cardiovascular Proteomics Center. The authors thank Granzins Meat Market at New Braunfels, Texas for their help in this work. We also thank Dr. Coleen Witt from the Computational Biology Initiatives at UTSA for her help in this study and thank the RCMI facility center supported by Grant G12MD007591 from the National Institutes of Health.
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