title: Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts.
abstract: We examined whether blocking the MyD88 mediated pathway could protect myocardium from ischemia/reperfusion (I/R) injury by transfecting Ad5-dnMyD88 into the myocardium of rats (n=8) 3 days before the hearts were subjected to ischemia (45min) and reperfusion (4h). Ad5-GFP served as control (n=8). One group of rats was (n=8) subjected to I/R without transfection. Transfection of Ad5-dnMyD88 significantly reduced infarct size by 53.6% compared with the I/R group (15.1+/-3.02 vs 32.5+/-2.59) while transfection of Ad5-GFP did not affect I/R induced myocardial injury (35.4+/-2.59 vs 32.5+/-2.59). Transfection of Ad5-dnMyD88 significantly inhibited I/R-enhanced NFkappaB activity by 50% and increased the levels of phospho-Akt by 35.6% and BCL-2 by 81%, respectively. Cardiac myocyte apoptosis after I/R was significantly reduced by 59% in the Ad5-dnMyD88 group. The results demonstrate that both inhibition of the NFkappaB activation pathway and activation of the Akt signaling pathway may be responsible for the protective effect of transfection of dominant negative MyD88.
authors.affiliation: Department of Surgery, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Jim
authors.initials: J
authors.lastname: Kelley
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: I William
authors.initials: IW
authors.lastname: Browder
authors.forename: Race L
authors.initials: RL
authors.lastname: Kao
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D008297:Male; D053594:Myeloid Differentiation Factor 88; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011971:Receptors, Immunologic