Carotid atherosclerosis. Immunocytochemical analysis of the vascular and cellular composition in endarterectomies.

Papers dealing with rupture of carotid plaque surface are few in spite of the growing importance of the subject. The aim of this study was to analyze the cellular and vascular components of surgically excised carotid endarterectomies in order to obtain information about their role in the pathogenesis of the plaque rupture and intraplaque hemorrhage. Seventy-six surgical specimens of carotid endarterectomies were used for this study. The findings of immunophenotyping of the cellular constituents of the plaques were: 1) endothelial lining: the fibrous cap at the site of the rupture showed an eroded surface with loss of the endothelial lining. Conversely, in the remaining surface a continuous, not damaged row of endothelial cells stained with anti-CD31 and anti-CD34 was observed; 2) fibrous cap: the collagenous fibrous cap at the site of erosion was attenuated and the phenotypic characterization of the cells showed inflammatory components consisting mainly of macrophages (CD68 positive), 2/3 of the total infiltration. The remaining 1/3 was composed of T-lymphocytes and scarce B-lymphocytes. A close interaction between macrophages and capillaries and macrophages and T-lymphocytes was observed; 3) lipid cores: two different types of lipid cores could be depicted. Avascular or mildly vascularized lipid cores and highly vascularized, with neoformed vessels stained with CD34 and CD31. CD34 stained endothelia of all kind of vessels; conversely, neoformed vessels showed a weak stain with CD31. T-lymphocytes were found to be in close contact with neoformed vessels, and in some cases, migrating through the endothelial cells; 4) deeper layers of the plaque: the base and the shoulder of the plaques showed in 28/76 cases neoformed vessels, thin or thick walled, CD34 positive, generally surrounded by mild to extensive mononuclear infiltrates. Atherosclerotic plaques were found to belong to six different lesions: plaque rupture plus thrombosis (18/76, 23.6%), plaque rupture plus intraplaque hemorrhage plus thrombosis (18/76, 23.6%), intraplaque hemorrhage without plaque rupture (16/76, 21.0%), plaque rupture plus intraplaque hemorrhage (5/76, 6.5%), stable calcified non complicated plaque (14/76, 18.4%) and unstable, soft, non complicated plaque (5/76, 6.5%). The first four lesions were considered as "complicated lesions". Complicated plaques presented neoformed vessels in the periphery, shoulder and base of the plaque in 22/57 (38.5%) cases. Conversely only 1/14 (7.1%) of non complicated, stable calcified plaques presented neoformed vessels, (p < 0.05). Of note, the 5 causes of unstable, soft non complicated plaque presented neoformed vessels surrounding the plaque. In 10/57 (17.5%) complicated plaques unequivocal histological signs of old hemorrhages were found surrounding those vessels. Irrespective of presenting no rupture, 11/35 plaques showed a mononuclear infiltrate in the fibrous cap. In conclusion, rupture of carotid plaques (50% of the cases), is characterized by the presence of a macrophagic infiltration of the caps and by the direct apposition of T-lymphocytes to macrophages and a close relation of these cells to endothelial cells. This highly suggests a cell-to-cell interaction, which results in an inflammatory process. Intraplaque hemorrhage without rupture represented 21% of the endarterectomies. These lesions are not related to cap erosion, but to plaque vascularization. Most lipid cores were highly vascularized with neoformed vessels with macrophages and T-cells in close contact and in some cases disrupting the endothelium. The abrupt growing of the lipid core and/or an overproduction of oxygen free radicals could lead to the breakdown of core vessels and intraplaque hemorrhage.