Key result
Sequential endoarterial biopsy in a porcine shunt model of pulmonary arterial hypertension successfully identified time-related changes in vascular histology and gene expression over 180 days.
Why the study?
Does sequential endoarterial biopsy identify changes in histology and gene expression during the progression of pulmonary arterial hypertension in a porcine model?
Does sequential endoarterial biopsy identify changes in histology and gene expression during the progression of pulmonary arterial hypertension in a porcine model?
Sequential endoarterial biopsy in a porcine model of PAH successfully identifies stage-specific variations in gene expression, offering a potential method for discovering novel therapeutic targets and individualized therapies.
Endoarterial biopsy tracks molecular progression in porcine PAH; leaves open validation of targets for human therapy.
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 mRNA expression during the disease progression. Differentially expressed genes were then analyzed as potential pharmacological 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, and 180 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 histology and in the expression of several genes with known or investigational inhibitors and several novel genes for PAH. Gene dysregulation displayed time-related variations during disease progression. Endoarterial biopsy provides a new method of assessing pulmonary vascular histology and gene expression in PAH. This analysis could identify novel applications for existing and new PAH drugs. The detection of stage- and disease-specific variation in gene expression could lead to individualized therapies.
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Rothman et al. (2013) studied Pulmonary arterial hypertension (n=4). Sequential endoarterial biopsy in a surgical shunt model vs. Baseline (before surgery) was evaluated on Changes in histology and mRNA expression during disease progression. Sequential endoarterial biopsy in a porcine shunt model of pulmonary arterial hypertension successfully identified time-related changes in vascular histology and gene expression over 180 days.
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