Unstable angina activates myocardial heat shock protein 72, endothelial nitric oxide synthase, and transcription factors NFkappaB and AP-1.
OBJECTIVE
Unstable angina may improve the clinical outcome of acute myocardial infarction, but increases the morbidity and mortality of open heart surgery. We hypothetized that unstable angina influences the myocardium, and investigated the expression of the inducible heat shock protein 72 (HSP72), constitutive HSP73, and endothelial nitric oxide synthase (eNOS), and activation of the transcription factors NFkappaB and AP-1 in cardiac tissue.


METHODS
Biopsies were taken from the right atrium of 15 patients with unstable and 15 with stable angina undergoing coronary artery bypass grafting. Immunoblotting with monoclonal antibodies against HSP72, HSP73, and eNOS were performed on protein extracts, while nuclear proteins were assessed by electromobility shift assay.


RESULTS
When calculating the optical density of the bands, patients with unstable angina had more than twice as much HSP72 and eNOS as stable patients (P<0.005), while HSP73 was similar in both groups. Nuclear translocation of NFkappaB and AP-1 was found in patients with anginal pain shortly before surgery, but not in stable patients or in patients without symptoms for 4 days or more prior to surgery.


CONCLUSIONS
HSP72 and eNOS, which may be associated with cardioprotection in ischemic preconditioning, are increased in atrial tissue of patients with unstable angina. Activation of NFkappaB and AP-1, which regulate a battery of inflammatory genes, was found in hearts of unstable patients. NFkappaB activation may induce a myocardial proinflammatory state, possibly making the unstable myocardium more susceptible to the inflammation induced by open heart surgery.
Valen
G
G
Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, S-171 76, Stockholm, Sweden. guro.valen@cmm.ki.se
Hansson
G K
GK
Dumitrescu
A
A
Vaage
J
J
D000368:Aged; D000789:Angina, Unstable / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III