| Background:The secondary prevention is very important in patients with Stable Angina (SA), with the same treatment, some SA patients develop acute cardiovascular events (ACEs), while others do not in a very long period, why? Based on this question, National973Project leaded by Chen Keji academician presented a hypothesis of "blood-stasisâ†'toxin" etiology and pathogenesis in cardiovascular thrombotic diseases, they considered blood stasis syndrome (BSS) was the basic syndrome in the development of CHD. Toxin was generally formed and accumulated by long-time BSS that brewed heat, or transformed from other pathologic factors. If lasting for a long time, delayed treatment or mistreatment, the accumulated toxin could be suddenly triggered by external causes and injured the tissue. The conglutination of toxin and blood-stasis further obstructed the heart vessel and leaded to ACEs. Therefore,"blood-stasis&toxin causing catastrophe" is the main etiology and key pathogenesis in SA patients who develop ACEs. Chen Keji academician and his fellow researchers further concluded the clinical manifestations of "toxin syndrome" in patient with SA by lots of literature studies and a prospective cohort study, they also made up a diagnostic and quantitative standard for the patients with SA complicated by "potential toxin syndrome". It is the basic or primary theory for us to study further. However, how to transform between BSS and "toxin syndrome"? And what is the biological substance in this process? All these questions need to study further.The proteome is a subject studying all the proteins in a cell, a kind of tissue or an organism in specific conditions or at specific times, it aims to all proteins and all the changes of these proteins. The proteome is similar to syndromes of Traditional Chinese Medicine (TCM) for its dynamics, timeliness, spatiality, specificity, integrality and et al. Different syndromes certainly have different biological substance, therefore, syndrome proteomics has been an important method to study TCM syndromes because it can reveal the biological substance of syndromes and their changes. The proteome is a subject studying proteins which can reflect biological function immediately, it has given us a new approach for explaining physical activities and has been a life science frontier in the time of post genome. The proteome has conquered the non-linear relationship between protein and gene, and could interpret the internal relationship between TCM syndromes and the biological substance, so far, the proteome has been one of the most effective approaches for revealing biological essence of syndromes.Objectives:To find the relative proteins of "Blood-stasisâ†'toxin syndrome" pathogenesis transformation in the progress of CHD-BSS by comparing different diseases or syndromes in a cross sectional study and a cohort study, the ACEs should be considered in this study.Methods:We included patients in6different groups including CHD-BSS, CHD-nonBSS, nonCHD-BSS, nonCHD-nonBSS, AMI and traditional toxic syndrome, a1-year follow-up was performed in1269CHD-BSS patients for ACEs. Patients in AMI were defined as "toxin syndrome" group, and SA patients who appeared ACEs in1year follow-up were defined as "potential toxin syndrome" group. Matrix Assisted Laser Desorption Ionization/Time-of Flight Mass Spectroscopy (Maldi-Tof-MS) technology was used to analyze and identify the differential proteins through horizontal and longitudinal contrast in these groups, and the key proteins for CHD " blood-stasisâ†'toxin" were identified finally. Using ClinProTool2.1software to analysis the polypeptide mass spectrum, using BioworksBrowser3.3.1SP1to Sequest search, the database for researching is International Protein Index (IPI human v3.45fasta with71983entries).Resul ts:(1)16peptides were found for "CHD",2of16peptides showed higher expression and14peptides showed lower expression.(2) No peptide showed significant difference for "BSS"(P>0.05).76peptides was found for "CHD-BSS"(P≤0.05),28of76peptides showed higher expression and48peptides showed lower expression.(3)6peptides were found for "blood-stasisâ†'toxin" transformation, the mass including1945.31Da,1981.25Da,1071.55Da,4644.76Da,6631.28Da and9527.44Da.3peptides were considered as "non blood-stasisâ†'toxin", the mass including3883.4Da,6432.56Da and4230.19Da.5of9proteins were ident if ied. The express ion of Isoform HMW of Kininogen-1precursor (KNG1) and Peroxiredoxin-1(PRDX1) showed increased gradually in "FB-FA-D"; the expression of Isoform1of Fibrinogen alpha chain precursor(FGA) showed decreased gradually in "FB-FA-D"; the expression of Apol ipoprotein Cl (APO C1) and Serine protease inhibitor (SERPINA5) showed decreased gradually in "FB-FA-D" but showed increased temporarily in "Ffa-FF"(FA: Patients developed ACEs in1-year follow-up; FB: Patients did not developed ACEs in follow-up; D: Patients in AMI; FF: Blood sample in reexamination for patients in FA and their blood samples were storaged very well; Ffa: Blood sample in enrollment for patients in FF). KNG1and PRDX1were used for modeling using SNN to distinguish FA and FB, discrimination power for FA was90.2%, predictive values for FA was89.6%.(4)4peptides were found for distinguishing CHD "blood-stasis&toxin" and traditional "toxin syndrome", peptides in higher expression in CHD "blood-stasis&toxin" were2022.61Da and1062.13Da, peptides in higher expression in traditional "toxin syndrome" were2863.13Da and3540.44Da. LOC653879(Similar to Complement C3) was identified, it showed high expression in CHD "blood-stasis&toxin"Conclus ions:KNG1and PRDX1were identified as biomarker for "blood-stasiszâ†'toxin" pathogenesis transformation, which might be related to the blood coagulation, fibrinolysis, effect of bradykinin and oxidative stress; FGA, AP0C1and SERPINA5A were also identified as biomarker for "blood-stas isâ†'toxin" pathogenesis transformation but need to study further; Model made up by KNG1and PRDX1for distinguishing "high-risk" patients in SA was established but need to check in the further. |
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