DOI: 10.4103/2045-8932.109913Pulmonary
Circulation | January-March 2013 | Vol 3 | No 1
Vascular histomolecular analysis by sequential endoarterial
biopsy in a shunt model ofpulmonary hypertension
Authors
Abraham Rothman, Stephanie
Davidson, Robert G Wiencek, William N Evans, Humberto Restrepo, Valeri Sarukhanov,
Erkki Ruoslahti, Roy
Williams, David Mann
Source
ChildrenÕs Heart Center
Nevada,3006 S Maryland Pkwy, Ste 690, Las Vegas, NV 89109, USA. Email: arothman@childrensheartcenter.com.
Abstract
The molecular mechanisms of
pulmonary arterial hypertension (PAH) remain ill‑defined. The aims of this study were to obtain sequential
endoarterial biopsy samples in a surgical porcine model of PAH and assess
changes in histology and mRNAexpression during the disease progression.
Differentially expressed genes were then analyzed as potential harmacological
targets. Four
Yucatan micro‑pigs
underwent surgical anastomosis of the left pulmonary artery to the descending
aorta.Endovascular samples were obtained with a biopsy catheter at baseline
(before surgery) and from the left lung 7, 60, and180 days after surgery. RNA
was isolated from biopsy samples, amplified and analyzed. Dysregulated genes
were linked to
drugs with
potential to treat or prevent PAH. With the development of PAH in our model, we
identified changes in histologyand in the expression of several genes with
known or investigational inhibitors and several novel genes for PAH.
Genedysregulation displayed time‑related variations during disease progression. Endoarterial
biopsy provides a new methodof assessing pulmonary vascular histology and gene
expression in PAH. This analysis could identify novel applicationsfor existing
and new PAH drugs. The detection of stage‑ and disease‑specific variation in gene expression could lead
toindividualized therapies.