Artery Remodeling Under Mechanical Twist

Cardiovascular disease(CVD)such as hypertension,atherosclerosis and myocardial infarction became the leading cause of chronic disease morbidity and mortality worldwide.Arteries and veins in vivo are subjected to significant mechanical stresses generated by lumen blood flow,pressure,surrounding tissue tethering,and body movement.It has been well documented that mechanical stresses play important roles in regulating vascular cell biology,the vascular functions,and the pathological development of vascular diseases.Arteries and veins may lose their mechanical stability under mechanical loads.The stability of blood vessels under in vivo loads is essential to maintain their physiological functions.Blood vessels often experience torsion and twist along their axes.Twisting of blood vessels can occur naturally with body movement and due to surgical procedures requiring blood vessel manipulation.A twisted vessel can disrupt normal blood flow,damage the endothelial lining,causing ischemia to distal organs,and increase the risk for thrombosis.Therefore,better understanding the artery remodeling responses and relative underlying mechanism is essential complementary to the previous studies of arterial growth under stress and strain.In this study,we would conduct the research from 4 perspectives:(1)Numerical mechanical analysis of stress and strain distribution in arterial wall;(2)Use FEM to simulate the artery deformation process,verify the numerical calculation results and visualize the artery deformed shape;(3)Develop ex vivo organ culture experiment of twisted artery to study the artery remodeling in 3 d;(4)Develop innovative in vivo rat model of twisted artery to investigate the artery remodeling in 3 d,1 w,and 4 w.Base on these 4 perspective studies,we could elucidate the underlying mechanism of artery remodeling under twist.The mechanical analysis results show the principal stress with no significant change between control and twist arteries.Meanwhile,shear stress on ?-z plane in twisted arteries show significant increase compared with zero in control arteries.And the principal strain reorient from 0° to 4.6 ± 0.5° in twisted ex vivo porcine artery and 9.3 ± 3.5° in twisted in vivo rat arteries.After arteries cultured ex vivo for 3 days,results demonstrated significant artery wall remodeling: MMP-2 increased significantly;cell proliferations were significantly higher;IEL fenestrae area decreased but aspect ratio increased;ECs were significantly elongated and reoriented towards blood flow direction.The results from in vivo rat model experiments showed significant artery remodeling in time-dependent manner: cell proliferation increase significantly;MMP-2 and MMP-9 increased considerably;IEL fenestrae area increased significantly while shape elongated;ECs orientation changed time-dependently towards blood flow direction,the morphology elongated;the ratio of wall thickness to lumen increased significantly;C/E ratio decreased notably which imply the decrease of arterial stiffness.These results demonstrated that axial twist can stimulate in vivo artery remodeling.Our current results provide insight into the arterial remodeling under twist ex vivo and in vivo.These results shed light into the structural stability,anisotropic mechanical behavior of arteries,cells responses and ECM responses under torsion.Understanding of twist behavior and remodeling under torsion enriches our knowledge of vascular biomechanics,provides insight into pathology of twisted blood vessels and vein grafts,and will also be useful in elucidating translational and clinical significance and planning new surgical treatment techniques.