Potential diagnostic biomarkers in serum of idiopathic pulmonary arterial hypertension☆
Received 20 April 2009; accepted 26 July 2009. published online 25 August 2009.
Summary
Background
The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is unknown, and the syndrome of IPAH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis of IPAH and thus to study their role in the disease process.
Methods
A comparative proteomic analysis was used for clinical screening of serum proteins in 10 patients with IPAH and compared with 10 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with serum proteins between individual IPAH patients and controls.
Results
Nine proteins and their isoforms, including leucine-rich α-2-glycoprotein (LRG), haptoglobin precursor, albumin isoform 2, transferrin variant, C3 complement, hydroxypyruvate reductase isoform 1, RAF1, fibrinogen isoformγ-A and fibrinogen isoformγ-B showed significant changes in serum of IPAH patients compared with controls by proteomic analysis. And significant higher serum levels of LRG in IPAH patients compared with controls were found by ELISA. Correlation analysis disclosed a significant association between serum LRG concentrations and New York Heart Association (NYHA) functional class (r=0.71, P<0.01) and cardiac output (CO) (r=−0.65, P<0.01).
Conclusions
These results indicate that there are significant differences in the expression of proteins in the serum of patients with IPAH and normal subjects. And the measurement of LRG, RAF1 and C3 complement levels in the serum may be helpful for the diagnosis of IPAH. In particular, LRG may be a specific prognostical biomarker of IPAH.
aResearch Center for Pathology and Physiology, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Bei-Li-Shi Road, Xi Cheng District, Beijing 100037, China
bPulmonary Vascular Diseases Center, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
dSino-German Laboratory for Molecular Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
Corresponding author. Tel./fax: +86 10 88398531.
Corresponding author.
☆ This work was funded by National Basic Research Program of China (973 program projects, program number: 2007CB512000, and project number: 2007CB512008 to J. Pu).
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