Figure 4.

Schematic representation of inflammatory circuits in previously radiated arteries. Previously radiated arterial segments exhibited an increased adventitial inflammatory response that was characterized by macrophage accumulation in the vicinity of an expanded of vasa vasorum. Previous studies have associated radiation with activation of the NF-κB pathway (6). The present study identified increased levels of 5-LO in radiated vs. nonradiated arterial segments, and that this enzyme was localized to perivascular adventitial macrophages. The 5-LO enzyme metabolizes arachidonic acid (AA) the LT precursor, LTA₄, which is then further metabolized to the chemotactic and proinflammatory LTB₄. In radiated arteries, adventitial LTB₄ was increased compared with the release from arterial medium. LTB₄ transduces proinflammatory effects by means of its high-affinity BLT₁ receptor, expressed on macrophages, smooth muscle cells (SMCs), and endothelial cells. Blocking 5-LO/LTB₄ signaling may represent a possible therapeutic adjunct to prevent late adverse cardiovascular effects of XRT.