Kline Jeffrey A, Steuerwald Nury M, Watts John A, Courtney Mark, Bonkovsky Herbert L
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.
Cannon Research, Carolinas Medical Center, Charlotte, NC, United States.
Thromb Res. 2015 Oct;136(4):769-74. doi: 10.1016/j.thromres.2015.08.017. Epub 2015 Aug 28.
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.
Prospective, noninterventional study.
Normotensive patients with suspected PE (n=87) who underwent CT pulmonary angiography and transthoracic Doppler-echocardiography.
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.
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.
Severity of TR varied inversely with hmox-1 expression, suggesting that hmox-1 expression affects pulmonary vascular reactivity after PE.
肺栓塞（PE）可导致心内溶血以及血浆血红蛋白和精氨酸酶-1升高，进而加重肺血管收缩。我们检验了这样一个假设，即与无三尖瓣反流（TR）的PE患者及无PE的患者相比，导致TR（提示肺动脉压较高）的PE患者白细胞中血红素加氧酶-1（hmox-1）的表达降低。
前瞻性非干预性研究。
87例疑似PE的血压正常患者，接受了胸部CT血管造影和经胸多普勒超声心动图检查。
显著TR定义为射流速度>2.7m/s。通过定量逆转录聚合酶链反应（rtPCR）评估白细胞中hmox-1、触珠蛋白、触珠蛋白相关基因、触珠蛋白受体、CD163和环氧化酶-2（cox-2）基因的表达，并检测hmox-1启动子的-413A→T单核苷酸多态性（SNP）和GT重复多态性。
在44例（50%）PE阳性患者中，22例有TR阳性，其平均肺血管阻塞率（39±32%）与TR阴性患者（28±26%，P=0.15）相比无显著差异。PE阳性且TR阳性的患者hmox-1和触珠蛋白基因的表达显著低于无PE阳性且无TR的患者。对于PE阳性（n=22）患者，hmox-1的表达与TR速度呈负相关（r(2)=0.45，P<0.001），而无PE患者则不然。hmox-1的表达在不同基因型之间无显著差异。各组间cox-2无差异，且与TR无相关性。
TR的严重程度与hmox-1的表达呈负相关，提示hmox-1的表达影响PE后的肺血管反应性。
