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Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair

Nicola Maschietto1, Luca Semplicini2, Giulio Ceolotto2, Arianna Cattelan2, Helen Poser3, Ilaria Iacopetti3, Gabriele Gerardi3, Giulia Maria De Benedictis3, Tommaso Pilla3, Daniele Bernardini3, Luca Aresu4, Stefania Rizzo5, Cristina Basso5, Andrea Semplicini2, Ornella Milanesi1

1 Pediatric Cardiology Unit, Department of Women’s and Children’s Health, University of Padua, Padova, Italy
2 Department of Medicine, University of Padua, Padova, Italy
3 Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy
4 Department of Comparative BioMedicine and Food Science, University of Padua, Padova, Italy
5 Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy

* Corresponding Author: Nicola Maschietto, MD, PhD, Pediatric Cardiology Unit, Department of Women’s and Children’s Health, University of Padua, Via Giustiniani 3, I – 35128 Padua, Padova, Italy. Email: email

Congenital Heart Disease 2017, 12(1), 74-83.

Abstract

Background: Stent implantation is the treatment of choice for adolescents and adults with aortic coarctation (CoAo). Despite excellent short-term results, 20%–40% of the patients develop arterial hypertension later in life, which was attributed to inappropriate response of the aortic baroreceptors to increased stiffness of the ascending aorta (ASAO), either congenital or induced by CoAo repair. In particular, it has been hypothesized that stent itself may cause or sustain hypertension. Therefore, we aimed to study the hemodynamic and structural impact following stent implantation in the normal aorta of a growing animal.
Methods: Eight female sheep completed the study and a stent was implanted in four. Every 3 mo we measured blood pressure of the anterior and posterior limbs and left ventricular function by echocardiography. Twelve months later invasive pressure was measured under baseline and simulated stress conditions. Expression of genes indicating oxidative stress (OS), endothelial dysfunction (ED) and stiffness, as well as pathological examination were performed in ascending (ASAO) and descending aorta (DSAO).
Results: SOD1 and MMP9 gene expression were higher in ASAO of the stented animals, compared to DSAO and controls, while NOS3 was decreased. No differences were found in blood pressure and echocardiographic parameters. No histological differences were found in the aorta of the two groups of animals.
Conclusions: Stent does not affect central and peripheral hemodynamics, cardiac structure and function even in the long term. However, the finding of markers of OS and increased stiffness of ASAO, proximal to the stent, points to molecular mechanisms for increased cardiovascular risk of patients with stented CoAo.

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Maschietto, N., Semplicini, L., Ceolotto, G., Cattelan, A., Poser, H. et al. (2017). Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair. Congenital Heart Disease, 12(1), 74–83.



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