Diverse forms of pulmonary hypertension remodel the arterial tree to a high shear phenotype

Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H405-17. doi: 10.1152/ajpheart.00144.2014. Epub 2014 May 23.


Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2(-n/X) and the arterial area ratio β = 2(1-2/X). Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process.

Keywords: allometry; complexity; pulmonary hypertension.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Arterioles / pathology
  • Arterioles / physiopathology
  • Body Weight
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Hemodynamics*
  • Humans
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / physiopathology*
  • Models, Cardiovascular*
  • Phenotype
  • Pulmonary Artery / pathology
  • Pulmonary Artery / physiopathology*
  • Reproducibility of Results
  • Retrospective Studies
  • Stress, Mechanical
  • Vascular Remodeling*