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Anti-Inflammatory Effects of Different Drugs/Agents with Antioxidant Property on Endothelial Expression of Adhesion Molecules

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Atherosclerosis is a chronic inflammatory process. The adhesion of leukocytes to the vascular endothelium, mediated by endothelial cell adhesion molecules including vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, is the pivotal early event in atherogenesis. Inflammatory cytokines could activate redox-sensitive transcription factors and induce endothelial expression of adhesion molecules, which could be inhibited to various degrees by different antioxidants suggesting the potential role of endogenous reactive oxygen species (ROS) in atherogenesis.

Many clinical drugs that against cardiovascular diseases have exhibited antioxidant effects; these drugs simultaneously inhibit endothelial adhesion molecule expression, such as aspirin, probucol, HMG-CoA reductase inhibitors, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, peroxisome proliferator-activated receptor α and γ ligands, calcium channel blockers, β-adrenergic blockers, etc. In addition, we have previously demonstrated that Ginkgo biloba extract, a Chinese herb with antioxidant activity, could significantly suppress inflammatory cytokine-stimulated endothelial adhesiveness to human monocytic cells by attenuating intracellular ROS formation, redox-senstive transcription factor activation, and VCAM-1 as well as ICAM-1 expression in human aortic endothelial cells. The similar anti-atherosclerosis effects have been also shown in other Chinese herbs or dietary supplements with antioxidant activity such as magnolol and salvianolic acid B either in vitro or in vivo.

Thus, oxidative stress is critical to endothelial adhesiveness in atherogenesis. The inhibition of endothelial adhesion molecule expression by drugs/agents with antioxidant activity may serve as a potential therapeutic strategy for clinical atherosclerosis.

Keywords: Adhesion molecules; antioxidants; atherosclerosis; endothelial cells; inflammation; oxidative stress

Document Type: Research Article


Affiliations: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2,Shih-Pai Road, Taipei, Taiwan, R.O. China.

Publication date: 2006-12-01

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  • Cardiovascular & Hematological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in cardiovascular and hematological disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cardiovascular and hematological disorders. As the discovery, identification, characterization and validation of novel human drug targets for cardiovascular and hematological drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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