Plexiform Arteriopathy in Rodent Models of Pulmonary Arterial Hypertension

Am J Pathol. 2019 Jun;189(6):1133-1144. doi: 10.1016/j.ajpath.2019.02.005. Epub 2019 Mar 26.


As time progresses, our understanding of disease pathology is propelled forward by technological advancements. Much of the advancements that aid in understanding disease mechanics are based on animal studies. Unfortunately, animal models often fail to recapitulate the entirety of the human disease. This is especially true with animal models used to study pulmonary arterial hypertension (PAH), a disease with two distinct phases. The first phase is defined by nonspecific medial and adventitial thickening of the pulmonary artery and is commonly reproduced in animal models, including the classic models (ie, hypoxia-induced pulmonary hypertension and monocrotaline lung injury model). However, many animal models, including the classic models, fail to capture the progressive, or second, phase of PAH. This is a stage defined by plexogenic arteriopathy, resulting in obliteration and occlusion of the small- to mid-sized pulmonary vessels. Each of these two phases results in severe pulmonary hypertension that directly leads to right ventricular hypertrophy, decompensated right-sided heart failure, and death. Fortunately, newly developed animal models have begun to address the second, more severe, side of PAH and aid in our ability to develop new therapeutics. Moreover, p38 mitogen-activated protein kinase activation emerges as a central molecular mediator of plexiform lesions in both experimental models and human disease. Therefore, this review will focus on plexiform arteriopathy in experimental animal models of PAH.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Disease Progression
  • Humans
  • Hypoxia / complications
  • Hypoxia / pathology
  • Indoles
  • MAP Kinase Signaling System / physiology
  • Mice
  • Mice, Knockout
  • Pulmonary Arterial Hypertension / etiology
  • Pulmonary Arterial Hypertension / metabolism
  • Pulmonary Arterial Hypertension / pathology*
  • Pulmonary Artery / pathology*
  • Pyrroles
  • Rats


  • Indoles
  • Pyrroles
  • Semaxinib