Heart failure increases protein expression and enzymatic activity of heme oxygenase-1 in the lung.
OBJECTIVE
Heart failure (HF) cell or siderophages are pulmonary macrophages that phagonicytize erythrocytes leaked from the congested capillaries due to HF. Degradation of erythrocytes and hemoglobin increases concentrations of heme in the lung. We hypothesized that the HF-induced increase in the concentration of heme up-regulates the expression and enzymatic activity of heme oxygenase (HO)-1 in the lung.


METHODS
Using the aortocaval (AC) fistula model of HF, we examined the following parameters 8-10 weeks after the creation of the fistula: morphological changes in the lung by Prussian blue iron and immunohistochemical staining, HO-1 protein expression and activity in the rat lungs, and concentrations of nitrite/nitrate (NO(x)(-)) and cyclic guanosine 3',5'-monophospate (cGMP) of the lung homogenates.


RESULTS
Iron-stained siderophages were observed only in the lungs of rats with AC fistula. Protein level and enzyme activity of HO-1 were significantly enhanced in the lung of HF rats. NO(x)(-) concentrations of the two groups were similar, but cGMP was elevated in the lung of AC fistula rats (0.34+/-0.06 vs. 0.89+/-0.20 pmol/mg protein, P=0.025). Staining of serial sections of the lung tissues demonstrated induction of HO-1 co-localized to iron-stained siderophages.


CONCLUSIONS
HF causes increased pulmonary HO-1 expression and activity, which emanates largely from siderophages. Up-regulation of HO-1 may have pulmonary protective in HF.
Lam
Chen F
CF
Departments of Anesthesiology, Mayo Clinic and Foundation, Rochester, MN, USA.
Croatt
Anthony J
AJ
Richardson
Darcy M
DM
Nath
Karl A
KA
Katusic
Zvonimir S
ZS
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D006152:Cyclic GMP / Q000378:metabolism; D006333:Heart Failure; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D008168:Lung / Q000378:metabolism*; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D009566:Nitrates; D011506:Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D006152:Cyclic GMP