Pulmonary Circulation
2017; Apr-Jun;7(2):455-464
DOI 10.1177/2045893217704206
Received: 12 January 2017
/ Accepted: 21 March 2017
Epub 2017 May 12
© 2017 Sage Journals
Assessment of microRNA and gene dysregulation in pulmonary
hypertension by endoarterial biopsy
Author
Abraham Rothman,
Humberto Restrepo, Valeri Sarukhanov, William N. Evans, Robert G. Wiencek Jr,
Roy Williams, Nicole Hamburger, Kylie Anderson, Jasmine Balsara and David Mann
Source
Children’s Heart
Center Nevada, 3006 S Maryland Pkwy, Ste 690, Las Vegas, Nevada 89109, USA. Email:
arothman@childrensheartcenter.com
Abstract
MicroRNAs
(miRNAs) may regulate a number of genes, each of which may have a variety of
functions. We utilized an endoarterial biopsy catheter to assess the
dysregulation of miRNAs in a porcine shunt model of pulmonary hypertension
(PH). Two Yucatan micropigs underwent surgical anastomosis of the left
pulmonary artery to the descending aorta. Endoarterial biopsy samples were obtained
at baseline, and at regular intervals during the progression of PH. RNA,
isolated from biopsy samples, was analyzed by Illumina miRNA expression
microarrays (containing _1200 human miRNAs), Affymetrix Porcine GeneChips,
Bioconductor, and
GeneSpring. We
examined a total of 925 genes in a PH whole genome microarray. Biopsy samples
showed that 39 miRNAs were downregulated and 34 miRNAs were upregulated
compared to baseline. The number of PH-associated genes reported to be controlled
by each of the dysregulated miRNAs was in the range of 1–113. The five miRNAs
that had the largest number of PH-associated genes were: miR-548c-3p,
miR-520d-3p, miR-130a-5p, miR-30a-3p, and miR-let-7g-3p. Several of the
dysregulated
miRNAs have been
associated with molecular pathways and biologic processes involved in PH. Among
29 miRNAs, which were predicted to be dysregulated by a systems biology
approach, we found four that were dysregulated in our porcine shunt model. An endoarterial
biopsy technique was successful in showing that a large number of miRNAs are
dysregulated in a porcine shunt model of PH. Many of these miRNAs control
multiple PH-associated genes, molecular pathways, and biologic processes.
Endoarterial biopsy offers potential experimental and clinical diagnostic
value.