Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study.
BACKGROUND
Oxidative stress (OS) and reduced nitric oxide (NO) bioavailability contribute to the pathogenesis of pulmonary hypertension (PH). Whether there are associations between OS and NO signaling biomarkers and whether these biomarkers are associated with the severity of PH remain unclear.


METHODS
Blood samples were collected from 35 healthy controls and 35 patients with pulmonary arterial hypertension (PAH, n = 12) or chronic thromboembolic pulmonary hypertension (CTEPH, n = 23). The mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were measured by right heart catheterization. We measured the derivative of reactive oxygen molecules (d-ROMs), biological antioxidant potential (BAP) and superoxide dismutase (SOD) by automatic biochemical analyzer, malondialdehyde (MDA) and asymmetric dimethylarginine (ADMA) by enzyme-linked immunosorbent assay. The relationship between oxidative-antioxidative biomarkers and ADMA, as well as their association with pulmonary hemodynamics, were analyzed.


RESULTS
Compared with age- and gender-matched controls, there was no significant difference of d-ROMs in PAH and CTEPH patients; MDA was increased in CTEPH patients (P = 0.034); BAP and SOD were decreased in PAH (P = 0.014, P < 0.001) and CTEPH patients (P = 0.015, P < 0.001); ADMA level was significantly higher in PAH (P = 0.007) and CTEPH patients (P < 0.001). No association between oxidative-antioxidative biomarkers and ADMA was found. Serum ADMA concentration was correlated with mPAP (r = 0.762, P = 0.006) and PVRI (r = 0.603, P = 0.038) in PAH patients.


CONCLUSIONS
The antioxidative potential and NO signaling are impaired in PAH and CTEPH. Increased serum ADMA level is associated with unfavorable pulmonary hemodynamics in PAH patients. Thus, ADMA may be useful in the severity evaluation and risk stratification of PAH.
Department of Pulmonary and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China. shuaizhang2012@126.com.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, People's Republic of China. shuaizhang2012@126.com.
Shuai
S
Zhang
Department of Pulmonary and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China. dryangting@qq.com.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, People's Republic of China. dryangting@qq.com.
Ting
T
Yang
Department of Pulmonary and Critical Care Medicine, Beijing Hospital, Beijing, People's Republic of China. xuxiaomao@163.com.|National Clinical Research Center of Respiratory Diseases, Beijing, People's Republic of China. xuxiaomao@163.com.
Xiaomao
X
Xu
Department of Laboratory Medicine, Beijing Hospital, Beijing, People's Republic of China. wangmenglj1@vip.tom.com.
Meng
M
Wang
Department of Pulmonary and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China. zhonglinye756@163.com.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, People's Republic of China. zhonglinye756@163.com.
Linye
L
Zhong
Department of Pulmonary and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China. yyh1031@sina.com.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, People's Republic of China. yyh1031@sina.com.
Yuanhua
Y
Yang
Department of Pulmonary and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China. zhaizhenguo2011@126.com.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Beijing, People's Republic of China. zhaizhenguo2011@126.com.
Zhenguo
Z
Zhai
National Clinical Research Center of Respiratory Diseases, Beijing, People's Republic of China. xiaofei@bjhmoh.cn.|Department of Cell Biology, Institute of Geriatrics, Beijing Hospital, Beijing, People's Republic of China. xiaofei@bjhmoh.cn.
Fei
F
Xiao
National Clinical Research Center of Respiratory Diseases, Beijing, People's Republic of China. cyh-birm@263.net.|Department of Respiratory Medicine, Capital Medical University, Beijing, People's Republic of China. cyh-birm@263.net.|China-Japan Friendship Hospital, Beijing, People's Republic of China. cyh-birm@263.net.
Chen
C
Wang
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D011669:Pulmonary Wedge Pressure / Q000502:physiology*; D015398:Signal Transduction; D014655:Vascular Resistance / Q000502:physiology
D015415:Biomarkers; D009569:Nitric Oxide