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



Abraham Rothman, Stephanie Davidson, Robert G Wiencek, William N Evans, Humberto Restrepo, Valeri Sarukhanov, Erkki Ruoslahti, Roy Williams, David Mann



Childrens Heart Center Nevada,3006 S Maryland Pkwy, Ste 690,  Las Vegas, NV 89109, USA. Email:



The molecular mechanisms of pulmonary arterial hypertension (PAH) remain illdefined. 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 micropigs 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 timerelated 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 diseasespecific variation in gene expression could lead toindividualized therapies.


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