Focal arterial inflammation is augmented in mice with a deficiency of the protein C gene.

Increased risk of thrombosis, with propitious conditions for fibrin deposition, along with upregulation of inflammation, are important factors that enhance plaque formation in atherosclerosis. Evidence supporting the role of anticoagulant protein C (PC) as an inflammatory agent has emerged, supplementing its well-known function as an anticoagulant. Thus, we sought to examine whether a PC deficiency would lead to an enhanced response to an acute arterial hyperplasic challenge. The presentation of early arterial inflammation was studied using a copper/silicone arterial cuff model of accelerated focal neointimal remodeling in mice with a heterozygous total deficiency of PC (PC+/-). Increased inflammation, cell proliferation, cell migration, fibrin elevation, and tissue necrosis were observed in the treated arteries of PC+/- mice, as compared to arteries of equally challenged age- and gender-matched WT mice. These results indicate that PC+/- mice subjected to this challenge displayed enhanced focal arterial inflammation and thrombosis, leading to larger neointimas and subsequent localized occlusion, as compared to their WT counterparts.

Fas ligand expression and its correlation with apoptosis and proliferation in Lobund-Wistar prostate carcinomas.

OBJECTIVE: The Fas (CD95) interaction with its receptor Fas ligand (FasL) is one of the main mechanisms of cell apoptosis. High expression of FasL has been consistently observed in a variety of human cancers. In this study, we evaluated FasL and its relationship with apoptosis and proliferation in Lobund-Wistar (L-W) cancers. The L-W rat strain develops spontaneous and induced adenocarcinomas in the anterior prostate and seminal vesicles. Although FasL expression has been observed in a subset of human prostate carcinomas, this multistage model allowed in vivo evaluation of subclones of malignant cells with a single genetic susceptibility. METHODS: Apoptosis was evaluated in spontaneous, induced and transplanted tumors as well as metastasis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique and transmission electron microscopy. Proliferating cell nuclear antigen (PCNA) and FasL expression were detected using immunohistochemistry and analyzed according to the number of positive cells and intensity of staining using a semiquantitive method. RESULTS: Apoptotic indexes were significantly higher in spontaneous tumors compared to induced (p < 0.008), transplanted tumors (p < 0.0112) and metastases (p < 0.009). TUNEL-positive cells were frequently observed in the leukocytic infiltrate of the stroma in transplanted carcinomas and metastases. These findings were confirmed by electron microscopy. FasL expression was not uniformly localized in L-W carcinomas and its highest expression was observed in transplanted tumors and metastasis (p < 0.005). Moreover, PCNA indices were directly correlated with cancers showing high FasL total scores (Hscores). CONCLUSIONS: In this model, high FasL expression was associated with cells displaying low apoptotic indexes and high PCNA index. Therefore, analysis of FasL may have clinical relevance in detecting the malignant potential of prostate cancers.