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A new animal model for pulmonary hypertension based on the overexpression of a single gene, angiopoietin-1  Danny Chu, MD, Christopher C Sullivan, MS,

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Presentation on theme: "A new animal model for pulmonary hypertension based on the overexpression of a single gene, angiopoietin-1  Danny Chu, MD, Christopher C Sullivan, MS,"— Presentation transcript:

1 A new animal model for pulmonary hypertension based on the overexpression of a single gene, angiopoietin-1  Danny Chu, MD, Christopher C Sullivan, MS, Lingling Du, MD, Augustine J Cho, BA, Masakuni Kido, MD, Paul L Wolf, MD, Matthew D Weitzman, PhD, Stuart W Jamieson, MB, FRCS, Patricia A Thistlethwaite, MD, PhD  The Annals of Thoracic Surgery  Volume 77, Issue 2, Pages (February 2004) DOI: /S (03)01350-X

2 Fig 1 Constitutive angiopoietin-1 transgene mRNA expression by polymerase chain reaction methods (A) and protein expression by Western blot assay (B) in lungs of rodents injected with adeno-associated virus-angiopoietin-1 (AAV-Ang-1) compared with rodents injected with adeno-associated virus-lacZ (AAV-lacZ). Lung gene expression measured at 1 and 2 months after viral gene transfer. (Ang-1 = angiopoietin-1, bp = base pair, GAPDH = glyceraldehyde-3-phosphate dehydrogenase, kD = kilodalton.) The Annals of Thoracic Surgery  , DOI: ( /S (03)01350-X)

3 Fig 2 (A) Photomicrograph of rodent lungs demonstrating severe hypertrophy/hyperplasia of medial layer of small arterioles measuring 40 μm compared with sham and control animals. (Bar = 25 μm.) (B) Photomicrograph of rodent lungs showing severe muscle hypertrophy of pulmonary arterioles measuring 300 μm compared with sham and control animals. (Bar = 150 μm.) (Hematoxylin & eosin stain, magnification ×40.) (Ang-1 = animals injected with adeno-associated virus-angiopoietin-1 [AAV-Ang-1]; lacZ = animals injected with adeno-associated virus-lacZ [AAV-lacZ]; Saline = animals injected with carrier saline.) The Annals of Thoracic Surgery  , DOI: ( /S (03)01350-X)

4 Fig 3 Pulmonary artery pressures of rodents at (Top) 30 and (Bottom) 60 days postgene delivery demonstrating persistent significantly elevated pressures of adeno-associated virus-angiopoietin-1 (AAV-Ang-1) injected animals compared with control animals. (Ang-1 = animals injected with AAV-Ang-1; lacZ = animals injected with adeno-associated virus-lacZ (AAV-lacZ); mm Hg = millimeters of mercury; PAD = pulmonary artery diastolic pressure; PAS = pulmonary artery systolic pressure.) The Annals of Thoracic Surgery  , DOI: ( /S (03)01350-X)

5 Fig 4 Whole lung gross Microfil pulmonary artery angiograms illustrate severe small vessel blunting in animals injected with adeno-associated virus-angiopoietin-1 (AAV-Ang-1) compared with control animals. (Left) Ang-1. (Right) lacZ. (Bar = 5 mm.) (Ang-1 = animal injected with AAV-Ang-1; lacZ = animal injected with adeno-associated virus-lacZ [AAV-lacZ].) The Annals of Thoracic Surgery  , DOI: ( /S (03)01350-X)

6 Fig 5 In situ RNA hybridization photomicrograph shows viral-specific angiopoietin-1 transcript being expressed in the walls of pulmonary arterioles. (Left) Ang-1. (Right) Saline. (Bar = 25 μm, nitro blue tetrazolium/5-bromo-4-chloro-3-indolyl-phosphate stain, magnification 40×.) The Annals of Thoracic Surgery  , DOI: ( /S (03)01350-X)


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