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Editorial
. 2019 Jan 4;124(1):6-8.
doi: 10.1161/CIRCRESAHA.118.314270.

In Search of the Second Hit in Pulmonary Arterial Hypertension

Peiran Yang  1 , Paul B Yu  1
Affiliations
Editorial

In Search of the Second Hit in Pulmonary Arterial Hypertension

Peiran Yang et al. Circ Res. .
No abstract available

Keywords: Editorials; chloride channels; guanine nucleotide exchange factors; humans; hypertension, pulmonary.

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Figures

Figure:
Figure:. Effects of CLIC4 in PAEC and PASMC.
CLIC4 expression and Arf6 activity are both increased in PH. In PAEC, CLIC4 acts via Arf6 to reduce BMPRII expression and signaling by promoting lysosomal degradation and reducing recycling of the receptor protein. CLIC4 also increases TGF-β and NFκB signaling, resulting in increased proliferation, inflammation and permeability; reduced apoptosis; dysregulated angiogenesis and vascular remodeling. In PASMC, BMPRII signaling maintains expression of CLIC4, responsible for activation of Rac1 and RhoA and cytoskeletal rearrangements required for hPASMC migration. Solid arrows denote regulatory effects, dotted arrows denote translocation. Blue text describes the effect of CLIC4 signaling on cell homeostasis. MHCIIA, myosin heavy chain IIA; ROS, reactive oxygen species.
See this image and copyright information in PMC

Comment on

  • CLIC4/Arf6 Pathway.
    Abdul-Salam VB, Russomanno G, Chien-Nien C, Mahomed AS, Yates LA, Wilkins MR, Zhao L, Gierula M, Dubois O, Schaeper U, Endruschat J, Wojciak-Stothard B. Abdul-Salam VB, et al. Circ Res. 2019 Jan 4;124(1):52-65. doi: 10.1161/CIRCRESAHA.118.313705. Circ Res. 2019. PMID: 30582444 Free PMC article.

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