Cardioprotective effect by tumor necrosis factor-alpha and interleukin-6 through late preconditioning in unstable angina patients.
BACKGROUND
It has recently been demonstrated that upregulation of proinflammatory cytokines plays an important role in induction of the late preconditioning in rodent models. The aim of this study was to determine if there was a late preconditioning effect caused by higher proinflammatory cytokines in unstable angina patients.


METHODS
TNFalpha and IL-6 levels in plasma before surgery were determined by an enzyme-linked immunosorbent assay. Biopsies of right atrial tissue were obtained from patients with unstable and stable coronary artery disease in conjunction with coronary artery bypass surgery. The two main transcription factors involved in the late preconditioning nuclear factor kappaB (NFkappaB), signal transducer and activator of transcription 3 (STAT3) were investigated by electromobility shift assay. The effector proteins in late preconditioning including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) were evaluated by immunoblotting as candidates for possible endogenous cardioprotective agents. Cardioprotective effects were assessed by creatine kinase MB (CK-MB) and cTnT leakage postoperatively.


RESULTS
We found parallel relationships between plasma cytokine levels, activated extent of transcription factors, expression quantities of effector proteins, and cardioprotective effects assessed by CK-MB and cTnT.


CONCLUSIONS
Upregulation of the proinflammatory cytokines in plasma by unstable angina induces late preconditioning effects and shifts the myocardium to a preconditioned phenotype upon exposure to impending stress.
Wang
Yongyi
Y
Department of Cardiovascular Surgery, The Second XiangYa Hospital, Central South University, ChangSha, HuNan, People's Republic of China. yongyi77@gmail.com
Yin
BangLiang
B
Liu
Sha
S
Xue
Song
S
D000368:Aged; D000789:Angina, Unstable / Q000601:surgery*; D002316:Cardiotonic Agents / Q000097:blood*; D001026:Coronary Artery Bypass; D052279:Creatine Kinase, MB Form / Q000097:blood; D051546:Cyclooxygenase 2 / Q000032:analysis; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000032:analysis; D019209:Troponin C / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D002316:Cardiotonic Agents; D015850:Interleukin-6; D008565:Membrane Proteins; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019209:Troponin C; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D052279:Creatine Kinase, MB Form