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Association of Soluble Markers with Various Stages and Major Events of Atherosclerosis

Address correspondence to James T. Wu, Ph.D., ARUP Laboratories, 500 Chipeta Way, Salt Lake City, Utah 84108, USA; tel 801 583 2787; fax 801 584 5207; e-mail: wuj{at}aruplab.com.

The purpose of this review is to identify soluble markers from the recent literature that facilitate the early prevention and early detection of atherosclerosis, and that may serve as therapeutic targets. Soluble markers associated with various stages and major events of atherosclerosis were identified. We divided the process of atherosclerosis into several stages, including stages for the early risk, plaque expansion, and stable and unstable angina–though excluding the end stage of myocardial infarction. For major events taking place prior to and during the progression of atherosclerosis we included events such as endothelial dysfunction in the artery, expression of adhesion molecules at the injured endothelium, continued inflammatory responses, oxidative stress, and ischemia. We found that reactions such as cell injury, adhesion, inflammation, and oxidative stress occur not only at the early stage of risk but persist throughout the process of atherosclerosis. Most markers associated with these major events are clustered together at any time of the disease. Few markers are characteristic of individual stages. We noted that reactions such as inflammation are continuously intensified with the progression of the disease. Finally, we underscore the importance of measuring a panel consisting of minimal numbers of multiple markers with the maximal sensitivity for early risk assessment, diagnosis, and prognosis. We envision that patterns characteristic of various stages of atherosclerosis may be identifiable with the use of the multiple markers described in this review.

Keywords: atherosclerosis, angina, ischemia, inflammation, oxidative stress, necrosis

Abbreviations: CAD, coronary artery disease; CHD, coronary heart disease; CVD, cardiovascular disease; CRP, C-reactive protein; GP, glutathione peroxidase; IMA, ischemia modified albumin; hsCRP, high sensitive CRP; ICAM, intracellular adhesion molecule; IL-8, interleukin 8; IL-6, interleukin 6; IGF-1, insulin-like growth factor-1; MCP-1, monocyte chemoattractant protein-1; M-CSF-1, macrophage-colony-stimulating factor-1; MDA-modified LDL, malondialdehyde-modified low-density lipoprotein; Lp-PLA2, lipoprotein derived phosphate lipase A2; MI, myocardial infarction; MMP, matrix metalloprotease; MPO, myeloperoxidase; NO, nitric oxide; OxLDL, oxidized low-density lipoprotein; 8-OHdG, 8-hydroxydeoxyguanosine; PVD, peripheral vascular disease; ROS, reactive oxygen species; SAA, serum amyloid protein A; tHcy, free and bound homocysteine; TGF-ß, transforming growth factor-beta; TNF-, tumor necrosis factor-alpha; VCAM, vascular cell-adhesion molecule; VEGF, vascular endothelial growth factor; VWF, von Willebrand factor

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