The purpose of this study was to analyze microRNA (miRNA) expression levels in pulmonary endoarterial biopsy samples during the progression of pulmonary arterial hypertension (PAH) in a surgical shunt porcine model.
Yucatan micropigs underwent surgical anastomosis of the left pulmonary artery to the descending aorta. Within one to two months the left pulmonary artery pressure increased from normal to approximately systemic level (Figure 1). Endoarterial biopsy samples were obtained percutaneously from 2–3 mm branch pulmonary arteries at baseline, and at regular intervals during the progression of PAH (Figure 2). Biopsy samples were procured with a novel endoarterial biopsy catheter (Figure 3), which allowed a correlation of the changes in miRNA expression to disease progression. RNA, isolated from biopsy samples, was loaded into illumina miRNA expression microarrays containing ∼1200 human miRNAs. Porcine and Homo sapiens miRNA sequences are very often highly conserved. Data were analyzed using Illumina Beadstudio, Bioconductor and GeneSpring (Figure 4). Three groups were defined: (1) Normal (baseline); (2) High Flow Low Pressure ‘HFLP’ and (3) High Pressure ‘PAH’ (Table 1). The groups were compared with baseline and the differentially regulated miRNAs were determined (P-value <0.5 as a cutoff).
MicroRNA analysis revealed pressure sensitive changes in miRNA expression. As the surgical shunt model of pulmonary hypertension progressed from a high flow low pressure (HFLP) physiology to PAH, several miRNAs became dysregulated (increased or decreased) relative to the baseline normal values (Tables 2,3,4,5,6,7).
Endoarterial biopsy provides a novel method to assess microRNA expression in hypertensive pulmonary arteries. A variety of microRNAs are dysregulated in a stage-specific manner during the progression of pulmonary arterial hypertension in an experimental model.
The detection of stage-specific dysregulated microRNAs in the pulmonary arterial wall could lead to stage-specific PAH diagnosis and development of new targets for PAH microRNA therapeutics.
David Mann, Shareholder Shareholder, Vascular BioSciences; Employee CEO, Vascular Biosciences; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Endoarterial Biopsy Catheter