Author + information
- Ahmed Fayyaz,
- Michael Sabbah,
- Surendra Dasari,
- Leigh Griffiths,
- Sarah Jenkins,
- Barry Borlaug,
- William Edwards and
- Margaret M. Redfield
Group 2 pulmonary hypertension (PH) due to heart disease induced pulmonary venous hypertension (PVH) is characterized by remodeling of pulmonary veins (PV) and arteries (PA). We hypothesized that different biologic pathways are altered in remodeled PV and PA in experimental PVH.
Left superior and common inferior PV were banded (PVH) or not (Sham) just proximal to left atrium in domestic piglets (mean weight 11.9 ± SD 3.0 kg). At sacrifice (weight 35.0 ± 18.0 kg), PV and PA (< 150 μm diameter) were perfusion labeled and subsequently laser capture micro-dissected from lung specimens of 6 PVH (mean PA pressure 45.2 ± 11.1 mmHg, pulmonary vascular resistance (PVR) 15.5 ± 12.2 wood units (WU)) and 6 Sham (mean PA pressure 19.3 ± 5.7 mmHg, PVR 2.1 ± 0.5 WU) pigs.
Vessel wall thickness (%) was increased in PVH (median (IQR), PA 39.0 (32.4, 56.1) %, PV 57.6 (31.1, 61.4) %) vs Sham (PA 15.5 (14.1, 16.7) %, PV 14.5 (14.1, 15.4) %) (p < 0.05 for all). Proteomic profiling used mass spectrometry-based label-free quantification and Ingenuity Pathways Analysis. More proteins were differentially expressed (vs Sham; FDR p < 0.05) in PV than PA (Figure Top). Three of the top 10 pathways altered in PVH are common to PV and PA and involve cellular proliferation. In PVs, 5 of the altered pathways are critically involved in epithelial-mesenchymal transition.
Unique mechanisms are involved in the pathogenesis of PA and PV remodeling in experimental Group 2 PH and suggest new drug targets for Group 2 PH.
Sunday, March 29, 2020, 8:51 a.m.-9:01 a.m.
Session Title: Highlighted Original Research: Pulmonary Hypertension and the Year in Review
Abstract Category: 35. Pulmonary Hypertension
Presentation Number: 904-10
- 2020 American College of Cardiology Foundation