mobic and Arteriosclerosis

Inflammation plays an important role in neointimal hyperplasia after vascular injury. COX-2 is a key mediator of inflammation and contributes to several inflammatory diseases. Although selective COX-2 inhibitors affect pathological conditions in inflammatory diseases, little is known about the effects on vascular remodeling after mechanical injury.. To clarify the role of COX-2 in vascular remodeling after arterial injury, we made a wire-injury model using C57BL/6J mice. These mice were orally administrated a selective COX-2 inhibitor twice a day. COX-2 mRNA expression was analyzed in injured femoral arteries.. COX-2 expression was markedly enhanced in the arterial wall on day 7; the expression was gradually decreased from day 14. In histopathological analyses, the COX-2 inhibitor significantly suppressed the progression of neointimal formation in comparison with non-treated mice. In an in vitro study, RNA was collected from macrophages after stimulation. The stimulation resulted in enhanced expression of IL-6 compared with the control, and the COX-2 inhibitor decreased this expression.. COX-2 is enhanced in the neointima after mechanical injury, and inhibition attenuated this. Therefore, regulation of COX-2 may be useful for preventing neointimal formation after coronary intervention.

Topics: Animals; Arteriosclerosis; Cell Line; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Progression; Endothelium, Vascular; Enzyme Induction; Femoral Artery; Interleukin-6; Macrophages; Male; Meloxicam; Mice; Mice, Inbred C57BL; RNA, Messenger; Stress, Mechanical; Thiazines; Thiazoles; Tunica Intima

Vascular smooth muscle is now recognized as an important site of mediator generation under inflammatory conditions. Indeed, the release of leukocyte activators, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-8, by human arterial smooth muscle cells has recently been demonstrated. However, the potential for venous cells to release GM-CSF has not been addressed. We have shown that human vascular smooth muscle cells express the "inflammatory" form of cyclooxygenase (COX), cyclooxygenase-2 (COX-2), when stimulated with cytokines. In some nonvascular cell types, the COX activity has been shown to regulate the release of GM-CSF and IL-8, although the nature of the isoform responsible was not addressed. We show that human venous smooth muscle cells, like their arterial counterparts, release GM-CSF after stimulation with IL-1beta. Similarly, both cell types released IL-8. Under the same conditions, we found that COX-2 activity suppressed GM-CSF, but not IL-8, release by both types of human vascular cells. Moreover, the prostacyclin mimetic, cicaprost, and the cAMP analogue, dibutyryl cAMP, inhibited GM-CSF release from these cells. These observations suggest that COX-2 activity suppresses GM-CSF release via a cAMP-dependent pathway in human vascular cells and illustrates a novel mechanism by which this enzyme can modulate immune and inflammatory events.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Arteriosclerosis; Aspirin; Bucladesine; Cells, Cultured; Cyclic AMP; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Epoprostenol; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Indans; Indomethacin; Interleukin-1; Interleukin-8; Isoenzymes; Mammary Arteries; Meloxicam; Membrane Proteins; Muscle, Smooth, Vascular; Neutrophils; Prostaglandin-Endoperoxide Synthases; Saphenous Vein; Sulfonamides; Thiazines; Thiazoles; Tumor Necrosis Factor-alpha