Beraprost sodium enhances neovascularization in ischemic myocardium by mobilizing bone marrow cells in rats.
Beraprost sodium, an orally active prostacyclin analogue, has vasoprotective effects such as vasodilation and antiplatelet activities. We investigated the therapeutic potential of beraprost for myocardial ischemia. Immediately after coronary ligation of Sprague-Dawley rats, beraprost (200 microg/kg/day) or saline was subcutaneously administered for 28 days. Four weeks after coronary ligation, administration of beraprost increased capillary density in ischemic myocardium, decreased infarct size, and improved cardiac function in rats with myocardial infarction. Beraprost markedly increased the number of CD34-positive cells and c-kit-positive cells in plasma. Also, four weeks after coronary ligation of chimeric rats with GFP-expressing bone marrow, bone marrow-derived cells were incorporated into the infarcted region and its border zone. Treatment with beraprost increased the number of GFP/von Willebrand factor-double-positive cells in the ischemic myocardium. These results suggest that beraprost has beneficial effects on ischemic myocardium partly by its ability to enhance neovascularization in ischemic myocardium by mobilizing bone marrow cells.
Miyahara
Yoshinori
Y
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan.
Ohnishi
Shunsuke
S
Obata
Hiroaki
H
Ishino
Kozo
K
Sano
Shunji
S
Mori
Hidezo
H
Kangawa
Kenji
K
Kitamura
Soichiro
S
Nagaya
Noritoshi
N
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects*; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
D002316:Cardiotonic Agents; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol