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

Congenit Heart Dis. 2017 Jan;12(1):74-83. doi: 10.1111/chd.12406. Epub 2016 Sep 7.

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.

Keywords: coarctation; endothelial dysfunction; hypertension; oxidative stress; stent implantation; stress genes.

MeSH terms

  • Animals
  • Aorta, Thoracic / growth & development
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Aorta, Thoracic / physiopathology*
  • Blood Pressure*
  • Echocardiography, Stress
  • Endothelium, Vascular / growth & development
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Endovascular Procedures / adverse effects*
  • Endovascular Procedures / instrumentation*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Hypertension / etiology*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Models, Animal
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress
  • Risk Factors
  • Sheep, Domestic
  • Stents*
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism
  • Time Factors
  • Vascular Stiffness
  • Ventricular Function, Left

Substances

  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase-1
  • Matrix Metalloproteinase 9