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


METHODS
Prospective, noninterventional study.


METHODS
Normotensive patients with suspected PE (n=87) who underwent CT pulmonary angiography and transthoracic Doppler-echocardiography.


METHODS
Significant TR was defined as a jet velocity >2.7m/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.


RESULTS
Of 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 (r(2)=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.


CONCLUSIONS
Severity of TR varied inversely with hmox-1 expression, suggesting that hmox-1 expression affects pulmonary vascular reactivity after PE.
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Physiology, Indiana University School of Medicine, Charlotte, NC, United States. Electronic address: jefkline@iu.edu.
Jeffrey A
JA
Kline
Cannon Research, Carolinas Medical Center, Charlotte, NC, United States.
Nury M
NM
Steuerwald
Cannon Research, Carolinas Medical Center, Charlotte, NC, United States.
John A
JA
Watts
Department of Emergency Medicine, Northwestern Feinberg School of Medicine, Chicago, IL, United States.
Mark
M
Courtney
Department of Internal Medicine Sections on Gastroenterology and Molecular Medicine & Translational Science, Chief of Hepatology, Wake Forest University School of Medicine, United States.
Herbert L
HL
Bonkovsky
D000208:Acute Disease; D005260:Female; D005342:Fibrinolysis; D006242:Haptoglobins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D014262:Tricuspid Valve Insufficiency / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
D006242:Haptoglobins; D051547:Heme Oxygenase-1
Fibrinolysis; Haptoglobin; Heme oxygenase; Hemolysis; Pulmonary hypertension