Regulation of lysyl oxidase isoforms in vascular tissues and cells by TNF-[alpha] and its receptor

Abstract

Lysyl oxidase (LOX) plays a crucial role in the biosynthesis and cross-linking of extracellular matrix proteins, collagen and elastin . It has been stated that LOX is up-regulated in cardiovascular diseases. Excessive accumulation and deposition of insoluble collagen fibers around vascular cells are leading to atherosclerosis and restenosis. In addition to LOX it self, four related genes has been described (LOX1-LOX4 ) and the expression of these genes were found in vascular tissues. Tumor Necrosis Factor-alpha (TNF-a) is a major pro-inflammatory cytokine that is a key regulator of the inflammatory response process. TNF-a can be associated with the development of atherosclerosis following vascular injury. Its cellular effects are exerted by activating the plasma membrane receptors Tumor Necrosis Factor Receptor-I (TNFR-1) and Tumor Necrosis Factor Receptor-2 (TNFR-2), which are expressed on cells and tissues. The purpose of this study is to investigate the role of TNFR-1 in the regulation of LOX and its isoforms in response to TNF-a in an atherosclerosis animal model in vivo and cell culture in vitro. [TRUNCATED]