The three mammalian lipoxygenases are named according to the carbon position (1, 2 or 3) at which they oxygenate arachidonic acid (4). There is increasing evidence that certain LO enzymes are involved in the pathogenesis and acceleration of atherosclerosis by inducing oxidation of LDL to its atherogenic form (5,6) and increasing the growth or migration of smooth muscle cells (1, 7-9). In addition, evidence suggests that a 12-LO protein plays a role in mediating angiotensin II (AII) induced vascular and adrenal actions (10-12). Recent studies indicate that at least two forms of 12-LO exist, i.e., pl 12-LO cloned from human erythroleukemia cells (2,13) and a porcine leukocyte 12-LO which has been isolated and cloned from porcine mononuclear cells, pituitary (14) and bovine tracheal cells (15).
Applicants have demonstrated the presence of a leukocyte type of 12-LO in human adrenal glomerulose cells (3). The human 15-LO has been purified from human and rabbit reticulocytes (16,17). The human platelet and porcine leukocyte type 12-LO share 65% amino acid homology (13). However, porcine leukocyte type 12-LO is highly homologous to human 15-LO (86%) (14). Recently, it has been shown that 15-LO is expressed in macrophages of human atherosclerotic lesions but not in unstimulated monocytes (18).
USPTO Backgrounds
USPTO Backgrounds