Preconditioning reduces tissue complement gene expression in the rabbit isolated heart.
Both preconditioning and inhibition of complement activation have been shown to ameliorate myocardial ischemia-reperfusion injury. The recent demonstration that myocardial tissue expresses complement components led us to investigate whether preconditioning affects complement expression in the isolated heart. Hearts from New Zealand White rabbits were exposed to either two rounds of 5 min global ischemia followed by 10 min reperfusion (ischemic preconditioning) or 10 microM of the ATP-dependent K+ (KATP) channel opener pinacidil for 30 min (chemical preconditioning) before induction of 30 min global ischemia followed by 60 min of reperfusion. Both ischemic and chemical preconditioning significantly (P < 0.05) reduced myocardial C1q, C1r, C3, C8, and C9 mRNA levels. Western blot and immunohistochemistry demonstrated a similar reduction in C3 and membrane attack complex protein expression. The K(ATP) channel blocker glyburide (10 microM) reversed the depression of C1q, C1r, C3, C8, and C9 mRNA expression observed in the pinacidil-treated hearts. The results suggest that reduction of local tissue complement production may be one means by which preconditioning protects the ischemic myocardium.
Tanhehco
E J
EJ
University of Michigan Medical School, Department of Pharmacology, Ann Arbor, Michigan 48109, USA.
Yasojima
K
K
McGeer
P L
PL
Washington
R A
RA
Kilgore
K S
KS
Homeister
J W
JW
Lucchesi
B R
BR
D000818:Animals; D003165:Complement System Proteins / Q000235:genetics*; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D019194:Ischemic Preconditioning; D008297:Male; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D017931:DNA Primers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012333:RNA, Messenger; D020110:Pinacidil; D003165:Complement System Proteins; D005905:Glyburide