Right Ventricular Angiogenesis is an Early Adaptive Response to Chronic Hypoxia-Induced Pulmonary Hypertension

Todd M. Kolb*, Jacelyn Peabody, Philip Baddoura, Jon Fallica, Jason R. Mock, Benjamin D. Singer, Franco R. D'Alessio, Mahendra Damarla, Rachel L. Damico, Paul M. Hassoun

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 cm2 vs. 4.9 ± 1.5 cm2; p = 0.01), and volume (0.0013 ± 0.0005 cm3 vs. 0.0006 ± 0.0001 cm3; 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.

Original languageEnglish (US)
Pages (from-to)724-736
Number of pages13
JournalMicrocirculation
Volume22
Issue number8
DOIs
StatePublished - Nov 1 2015

Keywords

  • Angiogenesis
  • Animal models
  • Pulmonary hypertension
  • Stereology

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Kolb, T. M., Peabody, J., Baddoura, P., Fallica, J., Mock, J. R., Singer, B. D., D'Alessio, F. R., Damarla, M., Damico, R. L., & Hassoun, P. M. (2015). Right Ventricular Angiogenesis is an Early Adaptive Response to Chronic Hypoxia-Induced Pulmonary Hypertension. Microcirculation, 22(8), 724-736. https://doi.org/10.1111/micc.12247