The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Vascular pathobiology of pulmonary hypertension

  • Eunate Gallardo-Vara
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, New Haven, Connecticut

    Department of Genetics, Yale University, New Haven, Connecticut
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  • Aglaia Ntokou
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, New Haven, Connecticut

    Department of Genetics, Yale University, New Haven, Connecticut
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  • Jui M. Dave
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, New Haven, Connecticut

    Department of Genetics, Yale University, New Haven, Connecticut
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  • Daniel G. Jovin
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, New Haven, Connecticut

    Department of Genetics, Yale University, New Haven, Connecticut
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  • Fatima Z. Saddouk
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, New Haven, Connecticut

    Department of Genetics, Yale University, New Haven, Connecticut
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  • Daniel M. Greif
    Reprint requests: Daniel M Greif, Department of Internal Medicine, Yale University, Yale Cardiovascular Research Center, New Haven, CT 06511, United States, Telephone: 203-737-6389. Fax: 203-737-6118.
    Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, New Haven, Connecticut

    Department of Genetics, Yale University, New Haven, Connecticut
    Search for articles by this author
Published:December 20, 2022DOI:
      Pulmonary hypertension (PH), increased blood pressure in the pulmonary arteries, is a morbid and lethal disease. PH is classified into several groups based on etiology, but pathological remodeling of the pulmonary vasculature is a common feature. Endothelial cell dysfunction and excess smooth muscle cell proliferation and migration are central to the vascular pathogenesis. In addition, other cell types, including fibroblasts, pericytes, inflammatory cells and platelets contribute as well. Herein, we briefly note most of the main cell types active in PH and for each cell type, highlight select signaling pathway(s) highly implicated in that cell type in this disease. Among others, the role of hypoxia-inducible factors, growth factors (e.g., vascular endothelial growth factor, platelet-derived growth factor, transforming growth factor-β and bone morphogenetic protein), vasoactive molecules, NOTCH3, Kruppel-like factor 4 and forkhead box proteins are discussed. Additionally, deregulated processes of endothelial-to-mesenchymal transition, extracellular matrix remodeling and intercellular crosstalk are noted. This brief review touches upon select critical facets of PH pathobiology and aims to incite further investigation that will result in discoveries with much-needed clinical impact for this devastating disease.



      BMP (bone morphogenetic protein), BMPR2 (bone morphogenetic protein receptor 2), CAV (caveolin), CD31 (cluster of differentiation 31), COX (cyclo-oxygenase), CXCL (C-X-C motif chemokine ligand), CXCR (C-X-C chemokine receptor), EC (endothelial cell), Eln (elastin), EndMT (endothelial-to-mesenchymal transition), ERK (extracellular signal-regulated kinases), ET (endothelin), Fox (Forkhead box protein), HES (hairy and enhancer of Split), HIF (hypoxia-inducible factor), IPAH (idiopathic pulmonary arterial hypertension), KLF (Kruppel-like factor), NO (nitric oxide), NOS (nitric oxide synthase), eNOS (endothelial nitric oxide synthase), PAEC (pulmonary artery endothelial cell), PAH (pulmonary arterial hypertension), PASMC (pulmonary artery smooth muscle cell), PDGFR (platelet-derived growth factor receptor), PDGF (platelet-derived growth factor), PH (pulmonary hypertension), RhoA (Ras homolog family member A), RVH (right ventricle hypertrophy), SMA (α-smooth muscle alpha), SMC (smooth muscle cell), SM22α (smooth muscle 22α), SNAI (snail-family transcription factor), TAZ (transcriptional co-activator with PDZ-binding motif), TGF (transforming growth factor), TNF (tumor necrosis factor), VEGF (vascular endothelial growth factor), VEGFR (vascular endothelial growth factor receptors), VHL (von-Hippel Lindau), YAP (Yes-associated protein)
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