Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair.
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.
Pediatric Cardiology Unit, Department of Women's and Children's Health, University of Padua, Padova, Italy.
Nicola
N
Maschietto
Department of Medicine, University of Padua, Padova, Italy.
Luca
L
Semplicini
Department of Medicine, University of Padua, Padova, Italy.
Giulio
G
Ceolotto
Department of Medicine, University of Padua, Padova, Italy.
Arianna
A
Cattelan
Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy.
Helen
H
Poser Dvm
Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy.
Ilaria
I
Iacopetti
Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy.
Gabriele
G
Gerardi
Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy.
Giulia Maria
GM
De Benedictis
Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy.
Tommaso
T
Pilla
Department of Animal Medicine, Production and Health, University of Padua, Padova, Italy.
Daniele
D
Bernardini
Department of Comparative BioMedicine and Food Science, University of Padua, Padova, Italy.
Luca
L
Aresu
Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy.
Stefania
S
Rizzo
Cardiovascular Pathology Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy.
Cristina
C
Basso
Department of Medicine, University of Padua, Padova, Italy.
Andrea
A
Semplicini
Pediatric Cardiology Unit, Department of Women's and Children's Health, University of Padua, Padova, Italy.
Ornella
O
Milanesi
D000818:Animals; D001013:Aorta, Thoracic / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure; D025401:Echocardiography, Stress; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D057510:Endovascular Procedures / Q000009:adverse effects* / Q000295:instrumentation*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D012307:Risk Factors; D034561:Sheep, Domestic; D015607:Stents; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D059289:Vascular Stiffness; D016277:Ventricular Function, Left
D052250:Nitric Oxide Synthase Type III; D000072105:Superoxide Dismutase-1; D020780:Matrix Metalloproteinase 9
coarctation; endothelial dysfunction; hypertension; oxidative stress; stent implantation; stress genes