Depletion of complement system immunity in patients with myocardial infarction

Yan,Wenwen; Che,Lin; Jiang,Jinfa; Yang,Fan; Duan,Qianglin; Song,Haoming; Liu,Xiaohong; Shen,Yuqin; Wang,Lemin

doi:10.3892/mmr.2016.5912

Depletion of complement system immunity in patients with myocardial infarction

Authors:
- Wenwen Yan
- Lin Che
- Jinfa Jiang
- Fan Yang
- Qianglin Duan
- Haoming Song
- Xiaohong Liu
- Yuqin Shen
- Lemin Wang
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Affiliations: Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China, Department of Laboratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China
Published online on: November 1, 2016 https://doi.org/10.3892/mmr.2016.5912
Pages: 5350-5356

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Abstract

The aim of the present study was to evaluate differences in the expression of complement system genes, and serum levels of CH50, C3 and C4 in peripheral blood mononuclear cells from patients with myocardial infarction (AMI), stable angina pectoris (SA) and controls. A total of 100 patients with AMI, 100 with SA and 100 clinical controls were recruited in the present study. In each group, 20 randomly selected individuals were examined using whole human genome microarray analysis to detect the expression of genes of the complement system. The serum levels of CH50, C3 and C4 were measured in all 300 subjects. In the patients with AMI, the expression levels of genes encoding C1qα, C1qβ, C1qγ, C1r, Factor P, C5a (complement component), CR1, integrin αM, integrin αX, integrin β2, C5aR, CRIg (complement receptors) and CD46, CD55 and CD59 (complement regulators) were significantly higher, compared with the respective genes in the SA patients and controls (P<0.05), whereas the mRNA levels of C1s, C7, C8β and C9 were the lowest in this group (P<0.05). No statistically significant differences were found in the gene expression levels of complement components or regulators between the SA and control groups. The serum levels of CH50, C3 and C4 were significantly increased in the AMI and SA groups, compared with the controls. In the AMI and SA groups, the complement system was activated. However, the differential mRNA expression of complement components, receptors and regulators in the AMI group suggested the dysfunction of the C5b-9 complex. The depression of complement system immunity in the patients with AMI may be associated with the pathogenesis of AMI.

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1	Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease, . Meeting the Challenges in Developing CountriesFuster V and Kelly BB: Promoting cardiovascular health in the developing world: A critical challenge to achieve global health. National Academies Press; Washington (DC): 2010
2	Evora PR, Nather J, Tubino PV, Albuquerque AA, Celotto AC and Rodrigues AJ: Curbing inflammation in the ischemic heart disease. Int J Inflam. 2013:1830612013. View Article : Google Scholar : PubMed/NCBI
3	Patzelt J, Verschoor A and Langer HF: Platelets and the complement cascade in atherosclerosis. Front Physiol. 6:492015. View Article : Google Scholar : PubMed/NCBI
4	Diepenhorst GM, van Gulik TM and Hack CE: Complement-mediated ischemia-reperfusion injury: Lessons learned from animal and clinical studies. Ann Surg. 249:889–899. 2009. View Article : Google Scholar : PubMed/NCBI
5	Speidl WS, Kastl SP, Huber K and Wojta J: Complement in atherosclerosis: Friend or foe? J Thromb Haemost. 9:428–440. 2011. View Article : Google Scholar : PubMed/NCBI
6	Esser AF: The membrane attack complex of complement. assembly, structure and cytotoxic activity. Toxicology. 87:229–247. 1994. View Article : Google Scholar : PubMed/NCBI
7	Francescut L, Steiner T, Byrne S, Cianflone K, Francis S and Stover C: The role of complement in the development and manifestation of murine atherogenic inflammation: Novel avenues. J Innate Immun. 4:260–272. 2012. View Article : Google Scholar : PubMed/NCBI
8	Széplaki G, Varga L, Füst G and Prohászka Z: Role of complement in the pathomechanism of atherosclerotic vascular diseases. Mol Immunol. 46:2784–2793. 2009. View Article : Google Scholar : PubMed/NCBI
9	Cubedo J, Padró T and Badimon L: Coordinated proteomic signature changes in immune response and complement proteins in acute myocardial infarction: The implication of serum amyloid P-component. Int J Cardiol. 168:5196–5204. 2013. View Article : Google Scholar : PubMed/NCBI
10	Mihlan M, Blom AM, Kupreishvili K, Lauer N, Stelzner K, Bergström F, Niessen HW and Zipfel PF: Monomeric C-reactive protein modulates classic complement activation on necrotic cells. FASEB J. 25:4198–4210. 2011. View Article : Google Scholar : PubMed/NCBI
11	Giasuddin ASM, ElMahdawi JM and ElHassadi FM: Serum complement (C3, C4) levels in patients with acute myocardial infarction and angina pectoris. Bangladesh Med Res Counc Bull. 33:98–102. 2007. View Article : Google Scholar : PubMed/NCBI
12	Iltumur K, Karabulut A, Toprak G and Toprak N: complement activation in acute coronary syndromes. APMIS. 113:167–174. 2005. View Article : Google Scholar : PubMed/NCBI
13	Kostner KM, Fahti RB, Case C, Hobson P, Tate J and Marwick TH: Inflammation, complement activation and endothelial function in stable and unstable coronary artery disease. Clin Chim Acta. 365:129–134. 2006. View Article : Google Scholar : PubMed/NCBI
14	Yasuda M, Takeuchi K, Hiruma M, Iida H, Tahara A, Itagane H, Toda I, Akioka K, Teragaki M, Oku H, et al: The complement system in ischemic heart disease. Circulation. 81:156–163. 1990. View Article : Google Scholar : PubMed/NCBI
15	Dobbin K and Simon R: Sample size determination in microarray experiments for class comparison and prognostic classification. Biostatistics. 6:27–38. 2005. View Article : Google Scholar : PubMed/NCBI
16	Thygesen K and Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for Universal Definition of Myocardial Infarction; Authors/Task Force Members Chairpersons, ; Thygesen K and Alpert JS: Third universal definition of myocardial infarction. J Am Coll Cardiol. 60:1581–1598. 2012. View Article : Google Scholar : PubMed/NCBI
17	Wiltgen M and Tilz GP: DNA microarray analysis: Principles and clinical impact. Hematology. 12:271–287. 2007. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Horváth Z, Csuka D, Vargova K, Kovács A, Molnár ÁA, Gulácsi-Bárdos P, Leé S, Varga L, Kiss RG, Préda I and Füst G: Elevated C1rC1sC1inh levels independently predict atherosclerotic coronary heart disease. Mol Immunol. 54:8–13. 2013. View Article : Google Scholar : PubMed/NCBI
20	Takahashi M, Mori S, Shigeta S and Fujita T: Role of MBL-associated serine protease (MASP) on activation of the lectin complement pathway. In Adv Exp Med Biol. 598:93–104. 2007. View Article : Google Scholar
21	Pesonen E, Hallman M, Sarna S, Andsberg E, Haataja R, Meri S, Persson K, Puolakkainen M, Ohlin H and Truedsson L: Mannose-binding lectin as a risk factor for acute coronary syndromes. Ann Med. 41:591–598. 2009. View Article : Google Scholar : PubMed/NCBI
22	Koch A, Melbye M, Sørensen P, Homøe P, Madsen HO, Mølbak K, Hansen CH, Andersen LH, Hahn GW and Garred P: Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. JAMA. 285:1316–1321. 2001. View Article : Google Scholar : PubMed/NCBI
23	Peterslund NA, Koch C, Jensenius JC and Thiel S: Association between deficiency of mannose-binding lectin and severe infections after chemotherapy. Lancet. 358:637–638. 2001. View Article : Google Scholar : PubMed/NCBI
24	Ali YM, Lynch NJ, Haleem KS, Fujita T, Endo Y, Hansen S, Holmskov U, Takahashi K, Stahl GL, Dudler T, et al: The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. PLoS Pathog. 8:e10027932012. View Article : Google Scholar : PubMed/NCBI
25	Low HZ, Hilbrans D, Schmidt-Wolf IG and Illges H: Enhanced CD21 expression and shedding in chronic lymphatic leukemia: A possible pathomechanism in disease progression. Int J Hematol. 96:350–356. 2012. View Article : Google Scholar : PubMed/NCBI
26	Asokan R, Banda NK, Szakonyi G, Chen XS and Holers VM: Human complement receptor 2 (CR2/CD21) as a receptor for DNA: Implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE). Mol Immunol. 53:99–110. 2013. View Article : Google Scholar : PubMed/NCBI
27	Nuutila J, Jalava-Karvinen P, Hohenthal U, Kotilainen P, Pelliniemi TT and Nikoskelainen J: Use of complement regulators, CD35, CD46, CD55 and CD59, on leukocytes as markers for diagnosis of viral and bacterial infections. Hum Immunol. 74:522–530. 2013. View Article : Google Scholar : PubMed/NCBI
28	Huang Y, Qiao F, Abagyan R, Hazard S and Tomlinson S: Defining the CD59-C9 binding interaction. J Biol Chem. 281:27398–27404. 2006. View Article : Google Scholar : PubMed/NCBI
29	Mayilyan KR: Complement genetics, deficiencies and disease associations. Protein Cell. 3:487–496. 2012. View Article : Google Scholar : PubMed/NCBI
30	Wu G, Hu W, Shahsafaei A, Song W, Dobarro M, Sukhova GK, Bronson RR, Shi GP, Rother RP, Halperin JA and Qin X: Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex. Circ Re. 104:550–558. 2009. View Article : Google Scholar