0360: Increased stiffness and cell-matrix interactions of abdominal aorta in two experimental non-hypertensive models: long-term chemical sympathectomized and sinoaortic-denervated rats

Abstract

Sinoaortic denervated (SAD) and chemically sympathectomized (SNX) rats are characterized by a decrease in arterial distensibility without hypertension and would thus be relevant for analyzing arterial wall stiffening independently of blood pressure level. The fibronectin network, which plays a pivotal role in cell matrix interactions, is a major determinant of arterial stiffness. We aim to determine in SAD and SNX rats the elastic properties of the arterial wall by evaluating in vivo the relationship between incremental elastic modulus by echotracking and circumferential wall stress, and the changes of cell-extracellular matrix links in the abdominal aorta, by studying fibronectin, vascular integrins receptors and ultrastructural features of the aorta by immunochemistry. We observed an increase in wall stiffness in both experimental conditions associated with different modifications of cell-extracellular matrix adhesion. In SAD rats, aortic hypertrophy was coupled with an increase of muscle cell attachments to its extracellular matrix via fibronectin and its a5-b1 integrin. In SNX rats, aortic hypotrophy was associated with up-regulation of av-b3 integrin and more extensive connections between dense bands and elastic fibers despite the disruption of the elastic lamellae. In aorta of SNX and SAD rats, different structural alterations are observed despite a similar arterial stiffness in absence of hypertension. An increase in avb3 or a5b1 integrins together with the already reported increase in the proportion of less distensible (collagen) to more distensible (elastin) components in both models, contribute to remodeling and stiffening of the abdominal aorta.