Extrahepatic Synthesis of FVII in Human Atheroma and Smooth Muscle Cells <i>in Vitro</i>

Abstract

The present series of experiments provide evidence that FVII is synthesized outside of the liver and is found in a variety of cells in normal and atherosclerotic vessels. In normal vessels FVII was localized to the endothelial cell layer and in adventitial fibroblasts at sites where tissue factor (TF) is also found. In early and advanced atherosclerotic lesions, FVII was mostly found in macrophage- rich regions colocalized with TF. Foam cells and macrophages in the necrotic core adjacent to the cholesterol clefts and foamy macrophages in early intimal thickenings all showed strong cytoplasmic staining with FVII antibodies. Although it is possible that FVII protein staining found in normal and atherosclerotic vessels originated from the blood, the finding of FVII mRNA by both in situ hybridization and RT-PCR suggests that these tissues are sites of FVII synthesis. Additional work demonstrated synthesis of FVII in a variety of tissues and smooth muscle cells and fibroblasts in vitro. The distribution of FVII synthesis in extrahepatic tissues and more recent data regarding thrombin-independent signaling as a consequence of FVII/TF binding may suggest the possibility of other cellular functions for this coagulation factor.