| Summary: | 博士 === 國立成功大學 === 基礎醫學研究所 === 95 === Atherosclerotic vascular disease is the major cause of morbidity and mortality in many developed countries. Central to the pathogenesis of atherosclerosis is the inflammation in the arterial wall. New approaches to atherosclerosis-related diseases include novel uses of proven treatments and development of innovative agents.
Statins are the most commonly prescribed agents for the treatment of hypercholesterolemia because of their efficacy in reducing low-density lipoprotein (LDL). Recent experimental and clinical evidence indicates the cholesterol-independent effects of statins. However, the genetic expression pattern changes in atherosclerotic lesions produced by statins are rarely studied. Cholesterol-fed apolipoprotein (apo) E-deficient mice were examined for the treatment effect of statin on aortic gene expression. The aortic gene expression affected by pravastatin was identified by the oligonucleotide microarray technology with Agilent gene chips. Microarray analysis of the expression of 20,281 murine genes in the aortas between the two groups indicated that 94 genes were significantly regulated. Thirty genes were up-regulated and 64 genes were down-regulated. Our study might provide insight into the clinical benefits of chronic statin treatment.
Macrophages play an important role in the inflammatory process in atherosclerosis. Opioid peptides have been shown to modulate immunoresponse. Naloxone is a non-selective antagonist of the opioid receptors. Dextromethorphan (DM) is the d-isomer of the codeine analog levophanol, a dextrorotatory morphinan. It is widely used as a cough suppressant in cold and cough medications with a high safety profile. Both of them could inhibit activation of microglia, the resident macrophage in nervous systems. We investigated whether naloxone and DM could reduce macrophage activation and influence atherosclerotic lesion formation in mice. In our study, we found that naloxone and DM pretreatment significantly suppressed the production of proinflammatory factors and superoxide in macrophage and mice after stimulation. The novel anti-inflammatory effect of naloxone and DM reduced the spontaneous aortic atherosclerotic lesion formation in apoE-deficient mice and the carotid neointima formation in C57BL6 mice receiving carotid ligation. The study of naloxone and DM generate many new and exciting hypotheses to be tested in the future.
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