Cyclooxygenase-2 and nuclear factor-kappaB in myocardium of end stage human heart failure.
Over the past three decades, numerous studies have shown diverse functional and morphological effects for prostanoids on cardiac myocytes with levels of prostanoids elevated in congestive heart failure. We examined the expression of cyclooxygenase-2 (COX-2) and activation of nuclear factor-kappaB (NF-kappaB) in failing human hearts. Expression of COX-2 and activation of NF-kappaB were examined in myocardial tissues from 27 patients with end stage heart failure, 2 septic patients, and 8 normal control subjects. There was little or no expression of COX-2 and NF-kappaB in the control hearts. There was abundant expression of COX-2 mRNA and protein in myocytes and inflammatory cells in areas of fibrotic scar compared with regions of normal morphology in all cases of heart failure, except in the cases with sepsis which showed abundant COX-2 throughout the myocardium. Sites of NF-kappaB activation were associated with those of COX-2 expression. We concluded that COX-2 expression and NF-kappaB activation are elevated in patients with congestive heart failure. Cellular induction of both molecules is associated with sites of inflammation and scar formation. (c)1999 by CHF, Inc.
Departments of Medicine and Pathology, The Montreal General Hospital and McGill University, Montreal, Quebec, Canada H3G 1A4.
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