Prostacyclin in vascular diseases. - Recent insights and future perspectives -.
Prostacyclin (PGI(2)) is one of the important vascular prostanoids, the effects of which counteract those of thromboxane (TXA(2)), and these 2 prostanoids provide an important balance in cardiovascular homeostasis. The clinical experience of COX-2 selective inhibitors having unexpected adverse effects in patients with cardiovascular risk has opened up a debate about the role of COX-2-derived prostanoids in vascular pathophysiology. PGI(2) is a major anti-atherogenic prostanoid produced by COX-2 in vascular cells, including endothelial and vascular smooth muscle cells. The balance between COX-2-derived PGI(2), COX-1-derived TXA(2), and other COX-2-mediated atherogenic prostanoids is a crucial factor in determining pathophysiological outcomes. Recent studies using stable PGI(2) analogs and genetically deficient mice have revealed novel effects of PGI(2) on its target cells, such as endothelial and endothelial progenitor cells. The role PGI(2) in the physiology and pathophysiology of vascular diseases is reviewed and the recent findings linking PGI(2), COX-2 and atherothrombosis are summarized.
Kawabe
Jun-ichi
J
Departments of Cardiovascular Regeneration and Innovation, Asahikawa Medical College, Asahikawa, Japan. kawabeju@asahikawa-med.ac.jp
Ushikubi
Fumitaka
F
Hasebe
Naoyuki
N
D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D042783:Endothelial Cells / Q000378:metabolism*; D011464:Epoprostenol / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D011464:Epoprostenol; D051545:Cyclooxygenase 1; C496512:Ptgs1 protein, mouse