Right Ventricular Angiogenesis is an Early Adaptive Response to Chronic Hypoxia-Induced Pulmonary Hypertension.
OBJECTIVE
Myocardial angiogenesis is presumed to play a role in RV adaptation to PH, though definitive evidence and functional correlations are lacking. We aimed to use definitive methods to correlate RV angiogenesis, hypertrophy, and function in a murine PH model.


METHODS
Mice were exposed to CH for 21 days to induce PH and RV remodeling. We used unbiased stereology and flow cytometry to quantify angiogenesis and myocyte hypertrophy, and pressure-volume loops to measure RV function.


RESULTS
Within seven days, RV-specific increases in total capillary length (10,576 ± 2574 cm vs. 6822 ± 1379 cm; p = 0.02), surface area (10 ± 3.3 cm(2) vs. 4.9 ± 1.5 cm(2) ; p = 0.01), and volume (0.0013 ± 0.0005 cm(3) vs. 0.0006 ± 0.0001 cm(3) ; p = 0.02) were observed, and RV EC proliferation increased nearly 10-fold. Continued exposure led to progressive RVH without additional angiogenesis. RV function was preserved, but activation of hypoxia-dependent gene expression was observed in both ventricles after 21 days.


CONCLUSIONS
Early RV remodeling in CH-PH is associated with RV angiogenesis and preserved RV function. Continued CH-PH is associated with RVH but not angiogenesis, leading to biventricular activation of hypoxia-dependent gene expression.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Todd M
TM
Kolb
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Jacelyn
J
Peabody
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Philip
P
Baddoura
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Jon
J
Fallica
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Jason R
JR
Mock
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Benjamin D
BD
Singer
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Franco R
FR
D'Alessio
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Mahendra
M
Damarla
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Rachel L
RL
Damico
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Paul M
PM
Hassoun
D000818:Animals; D006352:Heart Ventricles / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D020257:Ventricular Remodeling
angiogenesis; animal models; pulmonary hypertension; stereology