Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment.
The purpose of this study is to investigate whether an oxygen/ozone (O(2)/O(3)) mixture protects the heart from acute myocardial infarction through local involvement of endothelial nitric oxide synthase (eNOS) and endothelial progenitor cells (EPCs). Male Sprague-Dawley rats were subject to 25-min occlusion and 2-h reperfusion of the left descending coronary artery. O(2)/O(3) mixture was insufflated i.p. 30 min prior to ischemia/reperfusion (I/R) procedure at doses of 100, 150, and 300 microg/kg. Myocardial infarct size (IS) measurement and myocardial immunohistochemistry for EPCs were done. For these latter cells, immunoreactivities for CD34, and CD117/c-kit were assessed within the infarcted tissue. Moreover, cardiac eNOS was monitored. I/R in rats treated with O(2) produced an IS as a percentage of the area at risk (IS/AR) equal to 51 +/- 5%. I/R in rats treated with the O(2)/O(3) mixture showed reduced IS (for example, IS/AR for 150 microg/kg O(2)/O(3) was 35 +/- 2.1%; P < 0.01 vs. O(2)). The O(2)/O(3) cardio-protection was paralleled by an increased number of immunopositive particles per area for CD34 and CD117/c-kit. The increase of these markers was associated with an increase of cardiac eNOS expression as assayed by immunohistochemistry. Interestingly, N5-(1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO), a selective eNOS activity inhibitor (30 mg/kg s.c.), prior to O(2)/O(3) and I/R almost abolished the cardio-protection exerted by the O(2)/O(3) mixture. L-NIO also abolished the increase in immunostaining for CD-34 and CD117/c-kit as compared with the rats receiving O(2)/O(3) and I/R only. O(2)/O(3) mixture protects the heart from acute myocardial infarction through local increase of eNOS expression/activity and consequent EPCs recruitment.
Di Filippo
Clara
C
Department of Experimental Medicine, Second University of Naples, Via Costantinopoli 16, Naples, Italy. clara.difilippo@unina2.it
Luongo
Margherita
M
Marfella
Raffaele
R
Ferraraccio
Franca
F
Lettieri
Biagio
B
Capuano
Annalisa
A
Rossi
Francesco
F
D'Amico
Michele
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; C065027:N(G)-iminoethylornithine; D010126:Ozone; D009952:Ornithine; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen