LYSOPHOSPHATIDIC ACID IS THE CULPRIT MOLECULE INVOLVED IN BOTH ATHEROSCLEROSIS AND IN CANCER
Mohamad Navab, Ph.D.,
David Geffen School of Medicine, University of California Los Angeles, USA
Oxidized lipids have long been implicated in systemic inflammation and the resulting cardiovascular complications. One of the potent metabolites during lipid oxidation is lysophosphatidic acid (LPA). LPA has been known to be a potent growth promotor and more recently it was shown to be an atherogenic molecule. We have studied LPA in preclinical trials to determine the mode of generation of this molecule in the intestine and in the liver by feeding high cholesterol, high diet (Western diet, WD) and the effect of age and gender on its regulation. We have additionally studied the effect of the inhibitors of enzymes involved in the formation of LPA namely autotaxin. In other studies we have investigated the effect of feeding LPA to laboratory animals on the formation of lipid oxidation products in the intestine, in the circulation and in the liver determining the resulting effects on cardiovascular system. Our group, in separate studies, has looked into the effect of LPA in tumorigenesis in the intestine and metastasis to the lungs. We are exploring the pathways that contribute to both atherogenesis and to cancer through the actions of LPA.