Chronic skin-specific inflammation promotes vascular inflammation and thrombosis

J Invest Dermatol. 2012 Aug;132(8):2067-75. doi: 10.1038/jid.2012.112. Epub 2012 May 10.


Patients with psoriasis have systemic and vascular inflammation and are at increased risk for myocardial infarction, stroke, and cardiovascular death. However, the underlying mechanism(s) mediating the link between psoriasis and vascular disease is incompletely defined. This study sought to determine whether chronic skin-specific inflammation has the capacity to promote vascular inflammation and thrombosis. Using the KC-Tie2 doxycycline-repressible (Dox-off) murine model of psoriasiform skin disease, spontaneous aortic root inflammation was observed in 33% of KC-Tie2 compared with 0% of control mice by 12 months of age (P=0.04) and was characterized by the accumulation of macrophages, T lymphocytes, and B lymphocytes, as well as by reduced collagen content and increased elastin breaks. Importantly, aortic inflammation was preceded by increases in serum tumor necrosis factor-α, IL-17A, vascular endothelial growth factor, IL-12, monocyte chemotactic protein-1, and S100A8/A9, as well as splenic and circulating CD11b(+)Ly-6C(hi) pro-inflammatory monocytes. Doxycycline treatment of old mice with severe skin disease eliminated skin inflammation and the presence of aortic root lesion in 1-year-old KC-Tie2 animals. Given the bidirectional link between inflammation and thrombosis, arterial thrombosis was assessed in KC-Tie2 and control mice; mean time to occlusive thrombus formation was shortened by 64% (P=0.002) in KC-Tie2 animals; and doxycycline treatment returned thrombosis clotting times to that of control mice (P=0.69). These findings demonstrate that sustained skin-specific inflammation promotes aortic root inflammation and thrombosis and suggest that aggressive treatment of skin inflammation may attenuate pro-inflammatory and pro-thrombotic pathways that produce cardiovascular disease in psoriasis patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / pathology
  • Doxycycline / pharmacology
  • Flow Cytometry / methods
  • Gene Expression Regulation*
  • Inflammation*
  • Interleukins / metabolism
  • Macrophages / cytology
  • Mice
  • Monocytes / cytology
  • Psoriasis / complications
  • Psoriasis / metabolism*
  • Skin / metabolism
  • Skin / pathology*
  • Skin Diseases / metabolism
  • Thrombosis / metabolism*
  • Thrombosis / pathology
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukins
  • Tumor Necrosis Factor-alpha
  • interleukin-21
  • Doxycycline