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Heart Failure Increases Protein Expression and Enzymatic Activity of Heme Oxygenase-1 in the Lung FREE TO VIEW

Anthony Croatt; Darcy Richardson; Karl Nath, MD; Zvonimir Katusic, MD, PhD; Chen-Fuh Lam, MD*
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Mayo Clinic, Rochester, MN


Chest. 2004;126(4_MeetingAbstracts):774S. doi:10.1378/chest.126.4_MeetingAbstracts.774S
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PURPOSE:  Heart failure (HF) cells or siderophages are pulmonary macrophages that phagocyte the erythrocytes leaked from the congested capillaries due to HF. Degradation of erythrocytes and hemoglobin increases concentrations of heme in the lung. We hypothesized that HF-induced increase in the concentration of heme up-regulates the expression and enzymatic activity of heme oxygenase (HO)-1, which is a well-known cytoprotective protein, in the lung.

METHODS:  Rats received either aortocaval (AC) fistula (n=10) or sham (n=8) operation. Eight to ten weeks after inducing HF in the rats with the AC fistula due to chronic volume overload, we studied the following changes in the lungs: morphological changes by the Prussian blue iron and immunohistochemical staining; HO-1 protein expression and activity; concentrations of nitrite/nitrate (NOx-) and cyclic guanosine 3’,5’monophosphate (cGMP); and protein level of p38 mitogen activated protein kinase (MAPK).

RESULTS:  Iron-stained siderophages were observed only in the lung of rats with the AC fistula. Protein level and enzyme activity of HO-1 were significantly enhanced in the lung of rats with HF. cGMP was elevated in the lung of fistula rats (0.34±0.06 vs 0.89±0.20 pmol/mg protein; P= 0.02), but NOx- concentrations of the two groups were similar, indicating that elevated cGMP was most likely due to the up-regulation of HO-1. Protein expression and enzymatic activity of p38 MAPK, the other downstream signaling molecule of HO-1, were also increased in the lung of rats with AC fistula. Staining of serial sections of the lung tissues demonstrated induction of HO-1 colocalized to iron-stained siderophages.

CONCLUSION:  HF causes increased HO-1 expression and activity in the lung, which emanates largely from the pulmonary siderophages.

CLINICAL IMPLICATIONS:  Up-regulation of HO-1 may provide beneficial cytoprotective effects on the remodeling and cell survival in the lung of patients with HF.

DISCLOSURE:  C. Lam, None.

Tuesday, October 26, 2004

2:30 PM- 4:00 PM




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