Leukocyte expression of heme oxygenase-1 [hmox1] varies inversely with severity of tricuspid regurgitation in acute pulmonary embolism

•Severe acute pulmonary embolism (PE) causes intravascular hemolysis•Hemolysis releases free hemoglobin and heme, which scavenge nitric oxide•Induction of hmox-1 may be beneficial as it detoxifies heme and hmox-1 transcripts•Leukocyte expression of hmox-1 may be an adaptive response to PE

ObjectivePulmonary embolism (PE) can cause intracardiac hemolysis and increased plasma hemoglobin and arginase-1, which can worsen pulmonary vasoconstriction. We test the hypothesis that patients with PE that causes tricuspid regurgitation (TR), indicative of higher pulmonary arterial pressures, have decreased leukocyte expression of hmox-1 compared with patients with PE and no TR and patients without PE.DesignProspective, noninterventional study.PatientsNormotensive patients with suspected PE (n = 87) who underwent CT pulmonary angiography and transthoracic Doppler-echocardiography.MeasurementsSignificant TR was defined as a jet velocity > 2.7 m/s. Leukocyte expression of hmox-1, haptoglobin, haptoglobin related gene, the haptoglobin receptor, CD163 and cox-2 genes were assessed by quantitative rtPCR, and the hmox-1 promoter was examined for the − 413 A → T SNP and GT repeat polymorphisms.ResultsOf the 44 (50%) with PE +, 22 had TR +, and their mean pulmonary vascular occlusion (39 ± 32%) did not differ significantly from patients who were TR − (28 ± 26%, P = 0.15). Patients with PE + and TR + had significantly lower expression of hmox-1 and haptoglobin genes than patients without PE + and no TR. Expression of hmox-1 varied inversely with TR velocity (r2 = 0.45, P < 0.001) for PE + (n = 22) but not patients without PE. Hmox-1 expression did not vary significantly with genotype. Cox-2 did not differ between groups and had no correlation with TR.ConclusionsSeverity of TR varied inversely with hmox-1 expression, suggesting that hmox-1 expression affects pulmonary vascular reactivity after PE.

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