Atherosclerosis clinical trials role

PTKs have been implicated in the regulation of a variety of biological responses such as cell proliferation, migration, differentiation, and survival. They have been demonstrated to play significant roles in the development of many disease states, including immunodeficiency, atherosclerosis, psoriasis, osteoporosis, diabetes, and cancer. In recent clinical trials impressive antitumor effects of PTK inhibitors have been observed. In future, PTK inhibitors may therefore become important drugs for the treatment of specific cancers. 

Although ex vivo studies in a-tocopherol-supplemented humans have generally shown beneficial effects [30], clinical trials with a-tocopherol therapy have produced diverse results [31-36]. If a-tocopherol has no effects in humans with established coronary artery disease then either the role of LDL oxidation in human atherosclerosis or the ability of vitamin E to exert an antioxidant function in vivo may become highly questionable [37]. 

In summary, oxysterols are known to exist in atherosclerotic lesions and have been demonstrated in cell-culture experiments to have profound cellular effects that could influence the development, progression, and reversal of atherosclerosis. The key question in this field of research, however, is whether the concentrations of oxysterols in vivo are high enough to influence atherogenesis. Thus far, only the oxysterol-activated nuclear transcription pathway has been directly supported by in vivo data, and even in this case the precise roles and identification of the activating oxysterols in vivo have not yet been elucidated. Moreover, to the extent that oxysterols are generated in vivo and not just obtained from the diet, their role in human atherosclerosis has been questioned by clinical trials showing little or no protective effect of antioxidants on atherosclerotic coronary artery disease (K.J. Williams and E.A. Fisher, 2005). 

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