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PDGFRβ signalling regulates local inflammation and synergizes with hypercholesterolaemia to promote atherosclerosis

Author

Listed:
  • Chaoyong He

    (Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation)

  • Shayna C. Medley

    (Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation
    University of Oklahoma Health Sciences Center)

  • Taishan Hu

    (Immune Cell Development and Host Defense, Fox Chase Cancer Center)

  • Myron E. Hinsdale

    (University of Oklahoma Health Sciences Center
    Center for Veterinary Health Sciences, Oklahoma State University)

  • Florea Lupu

    (University of Oklahoma Health Sciences Center
    Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation)

  • Renu Virmani

    (CVPath Institute, Inc.)

  • Lorin E. Olson

    (Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation
    University of Oklahoma Health Sciences Center)

Abstract

Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (VSMCs). However, the direct effects of PDGF receptor β (PDGFRβ) activation on VSMCs have not been studied in the context of atherosclerosis. Here we present a new mouse model of atherosclerosis with an activating mutation in PDGFRβ. Increased PDGFRβ signalling induces chemokine secretion and leads to leukocyte accumulation in the adventitia and media of the aorta. Furthermore, PDGFRβD849V amplifies and accelerates atherosclerosis in hypercholesterolemic ApoE−/− or Ldlr−/− mice. Intriguingly, increased PDGFRβ signalling promotes advanced plaque formation at novel sites in the thoracic aorta and coronary arteries. However, deletion of the PDGFRβ-activated transcription factor STAT1 in VSMCs alleviates inflammation of the arterial wall and reduces plaque burden. These results demonstrate that PDGFRβ pathway activation has a profound effect on vascular disease and support the conclusion that inflammation in the outer arterial layers is a driving process for atherosclerosis.

Suggested Citation

  • Chaoyong He & Shayna C. Medley & Taishan Hu & Myron E. Hinsdale & Florea Lupu & Renu Virmani & Lorin E. Olson, 2015. "PDGFRβ signalling regulates local inflammation and synergizes with hypercholesterolaemia to promote atherosclerosis," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8770
    DOI: 10.1038/ncomms8770
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