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Modifications of human plasma apolipoprotein A1 in systemic autoimmune diseases and myocardial infarction: a comparative study

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Abstract

Aim

The study aims to obtain insight about the differences in cardiovascular disease risk presentation in rheumatoid arthritis, systemic lupus erythematosus and myocardial infarction pathologies based on modifications of monomeric plasma apolipoprotein A1 by proteomics.

Methodology

Blood samples were collected from myocardial infarction (n = 20), rheumatoid arthritis (n = 21) and systemic lupus erythematosus (n = 12) subjects along with normal controls (n = 13) for this study. Plasma ApoA1-oxidized modifications in each group were assessed by targeted proteomics and compared. Lipid profile, myeloperoxidase levels and few immunological parameters were also assessed.

Results

Very low density lipoprotein levels were high in all cases, while triglyceride/HDL ratio was twofold high in autoimmune diseases. Levels of MPO in RA cases were ~ 1.5-fold high, while SLE showed modest MPO levels compared to controls. Neutrophil counts were high in RA, while monocyte count was high in SLE. Proteomic investigation depicted equal ratio of methionine oxidation at position 86 and ~ 20% difference in pyroglutamination at positions 132 and 216 in RA and MI cases which may indicate a common phenomenon for cardiovascular disease. Pyroglutamination at position 216 in MI cases suggests the presence of auto-inflammation. Nitro-tyrosine and chloro-tyrosine residues were observed only in RA and SLE cases. Chloro-tyrosine modification at position 100 and nitro-tyrosine modification at position 166 were found relatively higher in RA cases.

Conclusion

Comparative analysis of all parameters disclosed distinctive pattern that may help in understanding the impact of inflammation and shed light on its relation with cardiovascular disease risk between the pathological groups.

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Abbreviations

ABCA1:

ATP binding cassette sub-family A member 1

ACR:

American College of Rheumatology

ApoA1:

Apolipoprotein A1

CVD:

Cardiovascular diseases

DAS:

Disease activity score

ESI:

Electrospray ionization

HDL:

High density lipoprotein

LCAT:

Lecithin cholesterol acyl transferase

MI:

Myocardial infarction

MPO:

Myeloperoxidase

MS-Q-ToF:

Mass spectrometer-quadrupole-time of flight

NADPH:

Nicotinamide adenine dinucleotide phosphate

ROS:

Reactive oxygen species

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

SLICC:

Systemic Lupus International Collaborating Clinics

References

  • Aletaha D et al (2010) Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581

    Article  Google Scholar 

  • Amaya-Amaya J, Montoya-Sánchez L, Rojas-Villarraga A (2014) Cardiovascular Involvement in Autoimmune Diseases. BioMed Research International [online]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142566/. Accessed 12 Nov 2017

  • Blasi C (2008) The autoimmune origin of atherosclerosis. Atherosclerosis 201(1):17–32

    Article  CAS  Google Scholar 

  • Brown KE, Brunt EM, Heinecke JW (2001) Immunohistochemical detection of myeloperoxidase and its oxidation products in Kupffer cells of human liver. Am J Pathol 159(6):2081–2088

    Article  CAS  Google Scholar 

  • Chistiakov DA, Orekhov AN, Bobryshev YV (2016) ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease. Lab Invest 96(7):708

    Article  CAS  Google Scholar 

  • DiDonato JA, Huang Y, Aulak K, Even-Or O, Gerstenecker G, Gogonea V, Wu Y, Fox PL, Tang WHW, Plow EF, Smith JD, Fisher EA, Hazen SL (2013) The function and distribution of apolipoprotein A1 in the artery wall are markedly distinct from those in plasma. Circulation 128(15). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882895/. Accessed 7 Mar 2018

    Article  CAS  Google Scholar 

  • DiDonato JA, Aulak K, Huang Y, Wagner M, Gerstenecker G, Topbas C, Gogonea V, DiDonato AJ, Tang WHW, Mehl RA, Fox PL, Plow EF, Smith JD, Fisher EA, Hazen SL (2014) Site-specific nitration of apolipoprotein A-I at tyrosine 166 is both abundant within human atherosclerotic plaque and dysfunctional. J Biol Chem 289(15):10276–10292

    Article  CAS  Google Scholar 

  • Durante A, Bronzato S (2015) The increased cardiovascular risk in patients affected by autoimmune diseases: review of the various manifestations. J Clin Med Res 7(6):379–384

    Article  CAS  Google Scholar 

  • Fernandes RMSN, da Silva NP, Sato EI (2012) Increased myeloperoxidase plasma levels in rheumatoid arthritis. Rheumatol Int 32(6):1605–1609

    Article  CAS  Google Scholar 

  • Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18(6):499–502

    CAS  PubMed  Google Scholar 

  • G AG, Kamalanathan AS, Vijayalakshmi MA, Venkataraman K (2018) Efficient purification of Apolipoprotein A1 (ApoA1) from plasma by HEA HyperCel™: an alternative approach. J Chromatogr B 1073:104–109

    Article  Google Scholar 

  • Garner B, Waldeck AR, Witting PK, Rye K-A, Stocker R (1998) Oxidation of high density lipoproteins II. Evidence for direct reduction of lipid hydroperoxides by methionine residues of apolipoproteins AI and AII. J Biol Chem 273(11):6088–6095

    Article  CAS  Google Scholar 

  • Kontush A (2014) HDL-mediated mechanisms of protection in cardiovascular disease. Cardiovasc Res 103(3):341–349

    Article  CAS  Google Scholar 

  • Levine RL, Mosoni L, Berlett BS, Stadtman ER (1996) Methionine residues as endogenous antioxidants in proteins. Proc Natl Acad Sci USA 93(26):15036–15040

    Article  CAS  Google Scholar 

  • Libby P (2002) Inflammation in atherosclerosis. Nature 420(6917):868–874

    Article  CAS  Google Scholar 

  • Libby P (2012) History of discovery: inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32(9):2045–2051

    Article  CAS  Google Scholar 

  • Matsuura E, Atzeni F, Sarzi-Puttini P, Turiel M, Lopez LR, Nurmohamed MT (2014) Is atherosclerosis an autoimmune disease? BMC Med 12:47

    Article  Google Scholar 

  • Millán J, Pintó X, Muñoz A, Zúñiga M, Rubiés-Prat J, Pallardo LF, Masana L, Mangas A, Hernández-Mijares A, González-Santos P, Ascaso JF, Pedro-Botet J (2009) Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag 5:757–765

    PubMed  PubMed Central  Google Scholar 

  • Morgan PE, Sturgess AD, Davies MJ (2005) Increased levels of serum protein oxidation and correlation with disease activity in systemic lupus erythematosus. Arthritis Rheum 52(7):2069–2079

    Article  CAS  Google Scholar 

  • Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet 349(9063):1436–1442

    Article  CAS  Google Scholar 

  • Nauseef WM (2014) Myeloperoxidase in human neutrophil host defense. Cell Microbiol 16(8):1146–1155

    Article  CAS  Google Scholar 

  • O’Neill SG, Giles I, Lambrianides A, Manson J, D’Cruz D, Schrieber L, March LM, Latchman DS, Isenberg DA, Rahman A (2010) Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 62(3):845–854

    Article  Google Scholar 

  • Pagano S, Gaertner H, Cerini F, Mannic T, Satta N, Teixeira PC, Cutler P, Mach F, Vuilleumier N, Hartley O (2015) The human autoantibody response to apolipoprotein A-I is focused on the C-terminal Helix: a new rationale for diagnosis and treatment of cardiovascular disease? PLoS One 10(7):e0132780

    Article  Google Scholar 

  • Pechlaner R, Tsimikas S, Yin X, Willeit P, Baig F, Santer P, Oberhollenzer F, Egger G, Witztum JL, Alexander VJ, Willeit J, Kiechl S, Mayr M (2017) Very-low-density lipoprotein-associated apolipoproteins predict cardiovascular events and are lowered by inhibition of APOC-III. J Am Coll Cardiol 69(7):789–800

    Article  CAS  Google Scholar 

  • Petri M et al (2012) Derivation and validation of systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686

    Article  Google Scholar 

  • Rosenson RS, Brewer HB, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR (2016) Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol 13(1):48–60

    Article  CAS  Google Scholar 

  • Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126

    Article  CAS  Google Scholar 

  • Shao B, Bergt C, Fu X, Green P, Voss JC, Oda MN, Oram JF, Heinecke JW (2005) Tyrosine 192 in apolipoprotein A-I is the major site of nitration and chlorination by myeloperoxidase, but only chlorination markedly impairs ABCA1-dependent cholesterol transport. J Biol Chem 280(7):5983–5993

    Article  CAS  Google Scholar 

  • Shao B, Cavigiolio G, Brot N, Oda MN, Heinecke JW (2008) Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I. Proc Natl Acad Sci USA 105(34):12224–12229

    Article  CAS  Google Scholar 

  • Shao B, Oda MN, Oram JF, Heinecke JW (2010) Myeloperoxidase: an oxidative pathway for generating dysfunctional HDL. Chem Res Toxicol 23(3):447–454

    Article  CAS  Google Scholar 

  • Shevchenko A, Tomas H, Havli J, Olsen JV, Mann M (2007) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. https://doi.org/10.1038/nprot.2006.468

    Article  Google Scholar 

  • Smith CK, Vivekanandan-Giri A, Tang C, Knight JS, Mathew A, Padilla RL, Gillespie BW, Carmona-Rivera C, Liu X, Subramanian V, Hasni S, Thompson PR, Heinecke JW, Saran R, Pennathur S, Kaplan MJ (2014) Neutrophil extracellular trap-derived enzymes oxidize high-density lipoprotein: an additional proatherogenic mechanism in systemic lupus erythematosus. Arthritis Rheumatol 66(9):2532–2544

    Article  CAS  Google Scholar 

  • Sreeja SA, Manoharan A, Venkataraman K (2018) Oxidized lipoproteins as the diagnostic target for cardiovascular diseases. Curr Sci 115:1276–1286

    Article  CAS  Google Scholar 

  • Steinberg D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272(34):20963–20966

    Article  CAS  Google Scholar 

  • Symmons DPM, Gabriel SE (2011) Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol 7(7):399–408

    Article  Google Scholar 

  • Szekanecz Z, Kerekes G, Végh E, Kardos Z, Baráth Z, Tamási L, Shoenfeld Y (2016) Autoimmune atherosclerosis in 3D: how it develops, how to diagnose and what to do. Autoimmun Rev 15(7):756–769

    Article  CAS  Google Scholar 

  • Teixeira PC, Ducret A, Ferber P, Gaertner H, Hartley O, Pagano S, Butterfield M, Langen H, Vuilleumier N, Cutler P (2014) Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases. J Biol Chem 289(41):28249–28259

    Article  CAS  Google Scholar 

  • Telles RW, Ferreira GA, da Silva NP, Sato EI (2010) Increased plasma myeloperoxidase levels in systemic lupus erythematosus. Rheumatol Int 30(6):779–784

    Article  CAS  Google Scholar 

  • Terkeltaub R (2014) ApoA-I at the interface of vascular inflammation and arthritis. Arterioscler Thromb Vasc Biol 34(3):474–476

    Article  CAS  Google Scholar 

  • Undurti A, Huang Y, Lupica JA, Smith JD, DiDonato JA, Hazen SL (2009) Modification of high density lipoprotein by myeloperoxidase generates a pro-inflammatory particle. J Biol Chem 284(45):30825–30835

    Article  CAS  Google Scholar 

  • Vivekanandan-Giri A, Slocum JL, Byun J, Tang C, Sands RL, Gillespie BW, Heinecke JW, Saran R, Kaplan MJ, Pennathur S (2013) High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis. Ann Rheum Dis 72(10):1725–1731

    Article  CAS  Google Scholar 

  • Wong YQ, Binger KJ, Howlett GJ, Griffin MDW (2010) Methionine oxidation induces amyloid fibril formation by full-length apolipoprotein A-I. Proc Natl Acad Sci USA 107(5):1977–1982

    Article  CAS  Google Scholar 

  • Zheng L, Nukuna B, Brennan M-L, Sun M, Goormastic M, Settle M, Schmitt D, Fu X, Thomson L, Fox PL, Ischiropoulos H, Smith JD, Kinter M, Hazen SL (2004) Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Investig 114(4):529–541

    Article  CAS  Google Scholar 

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Acknowledgements

The authors like to thank Ms. Renuka S and Ms. Dharani of ChanRe Rheumatology and Immunology Center and Research, Bangalore, for sample and clinical data collection. Two authors AG and VP would like to thank VIT, Vellore for providing infrastructure and support. The study was funded by BIRAC-CEFIPRA-French Embassy of India (Grant No.IFC/OxidizedHDL/2015/475).

Author information

Author notes

  1. Anand Manoharan

    Present address: Kanchi Kamakoti Childs Trust Hospital (KKCTH), Chennai, 600034, India

Authors and Affiliations

  1. Centre for Bioseparation Technology (CBST), Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, 632014, India

    G. Arungovind, A. S. Kamalanathan, Venkatesh Padmanabhan & Krishnan Venkataraman

  2. Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, 689101, India

    Anand Manoharan

  3. ChanRe Rheumatology and Immunology Center and Research, Bangalore, 560010, India

    Srikantiah Chandrashekara

  4. CHILDS Trust Medical Research Foundation (CTMRF), Chennai, Tamil Nadu, India

    Anand Manoharan

Authors
  1. G. Arungovind
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  2. A. S. Kamalanathan
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  3. Venkatesh Padmanabhan
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  4. Anand Manoharan
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  5. Srikantiah Chandrashekara
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  6. Krishnan Venkataraman
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Contributions

AG, ASK, SC and KV designed experiments. AG, ASK, VP and SC performed experiments. AG, ASK, VP, SC and KV analyzed the data. AM and SC contributed study samples and provided technical support. AG and ASK wrote the manuscript. All the authors read, corrected and revised the manuscript. KV secured funding from BIRAC-CEFIPRA-French Embassy of India.

Corresponding authors

Correspondence to A. S. Kamalanathan or Krishnan Venkataraman.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures in the study involving human participants were performed after obtaining informed consent from each participant. Samples were collected in accordance with the Declaration of Helsinki and the study was conducted after obtaining institutional ethical clearance.

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A. S. Kamalanathan and Krishnan Venkataraman share equal senior authorship.

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Arungovind, G., Kamalanathan, A.S., Padmanabhan, V. et al. Modifications of human plasma apolipoprotein A1 in systemic autoimmune diseases and myocardial infarction: a comparative study. J Proteins Proteom 10, 235–243 (2019). https://doi.org/10.1007/s42485-019-00018-6

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  • DOI: https://doi.org/10.1007/s42485-019-00018-6

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