title: Vascular histomolecular analysis by sequential endoarterial biopsy in a shunt model of pulmonary hypertension.
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 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.
authors: Children's Heart Center Nevada. Las Vegas, NV, USA ; Deptarment of Pediatrics, University of Nevada, School of Medicine, Las Vegas, NV, USA.
authors: Abraham
authors: A
authors: Rothman
authors: Stephanie
authors: S
authors: Davidson
authors: Robert G
authors: RG
authors: Wiencek
authors: William N
authors: WN
authors: Evans
authors: Humberto
authors: H
authors: Restrepo
authors: Valeri
authors: V
authors: Sarukhanov
authors: Erkki
authors: E
authors: Ruoslahti
authors: Roy
authors: R
authors: Williams
authors: David
authors: D
authors: Mann
keywords: endoarterial biopsy; pulmonary hypertension; vascular histomolecular analysis
references: Comp Med. 2011 Jun;61(3):258-62
references: 21819696
references: Am J Physiol Lung Cell Mol Physiol. 2004 Dec;287(6):L1241-7
references: 15286002
references: Circulation. 2011 Mar 22;123(11):1174-84
references: 21382894
references: Transplantation. 2003 Apr 15;75(7):960-5
references: 12698080
references: Circ Res. 2001 Mar 30;88(6):555-62
references: 11282888
references: Am J Respir Crit Care Med. 2004 Oct 15;170(8):911-9
references: 15215156
references: Circulation. 2005 Jun 7;111(22):2988-96
references: 15927975
references: Am J Physiol Heart Circ Physiol. 2010 Apr;298(4):H1235-48
references: 20081107
references: Eur J Cardiothorac Surg. 2003 Apr;23(4):513-7
references: 12694769
references: Nat Rev Cancer. 2006 Sep;6(9):735-41
references: 16915294
references: Respir Res. 2008 Feb 12;9:20
references: 18269757
references: Science. 1999 Oct 15;286(5439):531-7
references: 10521349
references: Circ Res. 2009 Jan 30;104(2):236-44, 28p following 244
references: 19074475
references: Int J Clin Pract Suppl. 2011 Jan;(169):19-28
references: 21176012
references: Circulation. 2010 Nov 16;122(20):2005-8
references: 21041686
references: Chest. 1998 Jul;114(1):241-50
references: 9674476
references: Eur Respir J. 2007 Dec;30(6):1103-10
references: 17804449
references: Circulation. 2004 Jun 22;109(24):2947-52
references: 15210611
references: Circ Res. 2006 Feb 3;98(2):172-5
references: 16456109
references: Circulation. 2004 Nov 30;110(22):3444-51
references: 15557369
references: Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H414-22
references: 11788387
references: J Am Coll Cardiol. 1996 Jan;27(1):218-24
references: 8522698
references: Am J Respir Crit Care Med. 2011 Jan 1;183(1):139-40
references: 21193794
references: J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):13S-24S
references: 15194174
references: Circulation. 2010 Aug 31;122(9):920-7
references: 20713898
references: Circulation. 2008 Jul 15;118(3):238-46
references: 18591436
references: Circulation. 2000 Nov 28;102(22):2781-91
references: 11094047
references: Exp Lung Res. 2005 Oct;31(8):783-806
references: 16368652
references: Am J Respir Crit Care Med. 2010 May 15;181(10):1106-13
references: 20460548
references: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S20-S31
references: 19555855