PURPOSE: The major radiobiological issue in determining the rationale for the use of radiation to inhibit vascular @entity256 is the identification of the target cell(s) and/or cytokine(s) responsible for neointimal @entity1373 and vascular remodeling. The central hypothesis of this report is that the macrophage/monocyte and PDGF are key elements in the process of neointimal @entity1373 seen following angioplasty, similar to their role in lesion formation and progression found in @entity731 thickening. Specific immunohistochemical and cytochemical stains were applied to a @entity35 carotid model in a temporal series after balloon angioplasty to determine macrophage activity vs. smooth muscle cell proliferation, the latter being classically thought to be the cell responsible for @entity256 . METHODS AND MATERIALS: Neointimal @entity1373 was created in an established @entity35 carotid artery model by a balloon catheter technique. Immediately following injury, treatment groups received irradiation via @entity1168 ( @entity1168 ) brachytherapy, the 192Ir source being placed externally to the vessel. Radiation was delivered to a length of 2 cm of the injured vessel at doses of 5, 10, and 15 Gy, and the animals were sacrificed at various time points following treatment (24 h to 6 months). Serial sections of tissue were stained immunohistochemically with the primary antibodies @entity19465 , mac-1, anti-PDGF, and @entity1918 . RESULTS: Immediately (24 h) postinjury, there is an apparent migration of macrophages seen in the adventitia; after 1 week, proliferation and migration of macrophages could be seen clearly within all the vessel layers, especially in the intima; by 3 weeks, when there was evidence of neointimal @entity1373 , macrophages could still be seen, mainly in the intima scattered among the smooth muscle cells and myofibroblasts, and to a lesser degree at 6 months. There was corresponding expression of PDGF, whenever and wherever there were zones of activation/neointimal @entity1373 . @entity1918 staining identified the smooth muscle cells distinct from the macrophages, and these SMCs exhibited activation in the neointimal @entity1373 zones at all later time points. Furthermore, we showed that radiation significantly reduced the macrophage population, while the onset of neointimal @entity1373 was accompanied by a return of the macrophage population. CONCLUSION: Our results suggest that the activated adventitial macrophage/monocyte are the key cells responsible for initiating the arterial neointimal @entity1373 and vascular remodeling developing postangioplasty as they are in the initiation and perpetuation of @entity1856 thickening. Irradiation delivered immediately postinjury is, therefore, highly effective, because the macrophage population is exquisitely radiosensitive.

Cellular and molecular mechanisms of radiation inhibition of XXXX . Part I: role of the macrophage and platelet-derived growth factor.

@entity1373 :: ('MESH:D006965', 'Disease') :: ['hyperplasia'] @entity256 :: ('MESH:D023903', 'Disease') :: ['restenosis'] @entity1918 :: ('25365(Tax:10116)', 'Gene') :: ['Alpha-smooth muscle actin', 'alpha-smooth muscle actin'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerotic'] @entity1168 :: ('MESH:D001919', 'Disease') :: ['HDR', 'high dose rate'] @entity1856 :: ('MESH:D058226', 'Disease') :: ['atheromatous'] @entity19465 :: ('25021(Tax:10116)', 'Gene') :: ['CD11b']
@entity256 :: (MESH:D023903,Disease) :: ['restenosis']
