Key result
Surgical abdominal aorta stenosis in rats induced distinct adaptive remodeling: prestenotic remodeling driven by increased wall tension and poststenotic remodeling driven by turbulent flow.
RCT
Randomized
Infradiaphragmatic aortic stenosis in rats induces distinct remodeling responses in prestenotic (hypertensive, increased wall tension) and poststenotic (normotensive, turbulent flow/low shear stress) segments.
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Rat model shows distinct stretch- vs flow-driven aortic remodeling; leaves open translation to human hypertension or coarctation.
OBJECTIVE: The present investigation was carried out to evaluate the relationship between local hemodynamic forces and intimal and medial remodeling in the proximal and distal segments of the arterial walls of rats in relation to severe infradiaphragmatic stenosis of the aorta. METHODS: Young male rats were divided randomly into an operated group, animals submitted to surgical abdominal aorta stenosis, and a sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. RESULTS AND CONCLUSIONS: Constricted aortas showed two distinct adaptive remodeling responses to hemodynamic stimuli induced by infradiaphragmatic coarctation. The first is remodeling in the hypertensive prestenotic segment with increased circumferential wall tension (CWT), associated with normal tensile stress, laminar flow/normal wall shear stress characterized by enlarged heterogeneous endothelial cells, elongated in the direction of the blood flow, diffusely distributed neointimal plaques, appearing as discrete bulging towards the vascular lumen and medial thickening. Our findings suggest that increased CWT caused by hypertension play a pivotal role in the remodeling of the prestenotic segment through biomechanical effects on oxidative stress and increased expression of transforming growth factor beta. The second is remodeling in the normotensive poststenotic segment with turbulent flow/low wall shear stress and normal CWT and tensile stress characterized by groups of endothelial cells with phenotypic alterations and focally distributed neointimal plaques, similar but many of them larger than those found in the prestenotic segments. Further studies are needed to determine how the mechanical forces of turbulent flow/low shear stress are detected and transduced into chemical signaling by the cells of the artery walls and then converted into pathophysiologically relevant phenotypic changes.
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Prado et al. (2006) conducted an RCT in Severe infradiaphragmatic stenosis of the aorta. Surgical abdominal aorta stenosis vs. Sham operation was evaluated on Intimal and medial remodeling in the proximal and distal segments of the arterial walls. Surgical abdominal aorta stenosis in rats induced distinct adaptive remodeling: prestenotic remodeling driven by increased wall tension and poststenotic remodeling driven by turbulent flow.
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