Biomarker profiling of plasma from acute coronary syndrome patients. Application of ProteinChip Array analysis.
OBJECTIVE
Acute coronary syndrome (ACS) is one of the leading causes of death in the world and remains a complex pathophysiologic process involving inflammatory, hemostatic and vascular processes. The purpose of this study was to identify unique proteomic biomarkers present in patients with ACS using a newly developed proteomic profiling technique, surface enhanced laser desorption/ionization (SELDI).


METHODS
Citrated plasma samples obtained from clinically confirmed cases of ACS (n=100) and age matched controls (n=25) were profiled using SELDI-time of flight (TOF)-mass spectrometry (Ciphergen Biosystems, Freemont, CA, USA). A strong anion exchange (SAX) ProteinChip Array was used to profile these samples. In addition to spectra profiles, protein density plots were be obtained from the generated molecular profile.


RESULTS
The SELDI profile in the molecular weight (MW) range of 0-150 kDa revealed a prominent 66.3 kDa albumin peak along with several distinct components at 28 kDa, 13.7 kDa and 6.5 kDa. Additional minor molecular components were also noted in the lower MW range (<6 kDa). There was a cluster of peaks between 10 and 12 kDa that were unique to the patients with ACS; about 1/3 of the ACS patients exhibited these peaks as evident in the ProteinChip Array spectrum. None of the age-matched controls exhibited the peaks in this MW range, nor did the normal human plasma pool that was used as an additional control. The relative intensity of these novel molecular components in the range of 10-12 kDa represent unique proteins/peptides which are generated in specific pathologic states associated with ACS.


CONCLUSIONS
These observations suggest that patients with ACS have a unique cluster of molecular components that are present in their SELDI profile. It might be possible to use these patterns to identify high-risk patients who may be more susceptible to the development of unstable plaque, which may eventually lead to myocardial infarction. Identification and characterization of these molecular components will also help in the understanding of the pathogenesis of ACS. These unique peaks may represent pathologic proteins, novel inflammatory mediators or protease cleavage products. Further studies need to be done to better characterize and identify these molecular components and their pathologic role in ACS.
Florian-Kujawski
M
M
Loyola University Medical Center, Maywood, IL, USA. mfloria@lumc.edu
Hussain
W
W
Chyna
B
B
Kahn
S
S
Hoppensteadt
D
D
Leya
F
F
Fareed
J
J
D000208:Acute Disease; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood*; D006801:Humans; D006900:Hydroxylation; D013058:Mass Spectrometry; D008970:Molecular Weight; D010455:Peptides / Q000378:metabolism; D040081:Protein Array Analysis; D011506:Proteins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013577:Syndrome
D015415:Biomarkers; D010455:Peptides; D011506:Proteins; D012709:Serum Albumin