Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

Helene Skjøt-Arkil; Rikke E Clausen; Lars M Rasmussen; Wanchun Wang; Yaguo Wang; Qinlong Zheng; Hans Mickley; Lotte Saaby; Axel C P Diederichsen; Jess Lambrechtsen; Fernando J Martinez; Cory M Hogaboam; Meilan Han; Martin R Larsen; Arkadiusz Nawrocki; Ben Vainer; Dorrit Krustrup; Marina Bjørling-Poulsen; Morten A Karsdal; Diana J Leeming

doi:10.1371/journal.pone.0060936

Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

Helene Skjøt-Arkil, Rikke E Clausen, Lars M Rasmussen, Wanchun Wang, Yaguo Wang, Qinlong Zheng, Hans Mickley, Lotte Saaby, Axel C P Diederichsen, Jess Lambrechtsen, Fernando J Martinez, Cory M Hogaboam, Meilan Han, Martin R Larsen, Arkadiusz Nawrocki, Ben Vainer, Dorrit Krustrup, Marina Bjørling-Poulsen, Morten A Karsdal, Diana J Leeming

Nutritional Immunology

15 Citations (Scopus)

Abstract

Background:Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two different diseases and if these fragments have the potential of being diagnostic biomarkers.Methods:Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope) generated at the amino acid position '552 in elastin by matrix metalloproteinase (MMP) -9/-12. A newly identified ELM neoepitope was generated by the same proteases but at amino acid position '441. The distribution of ELM-2 and ELM, in human arterial plaques and fibrotic lung tissues were investigated by immunohistochemistry. A competitive ELISA for ELM-2 was developed. The clinical relevance of the ELM and ELM-2 ELISAs was evaluated in patients with acute myocardial infarction (AMI), no AMI, high coronary calcium, or low coronary calcium. The serological release of ELM-2 in patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF) was compared to controls.Results:ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p<0.01). Levels of ELM were not significantly increased in these patients and no correlation was observed between ELM-2 and ELM. ELM-2 was not elevated in the COPD and IPF patients and was not correlated to ELM. ELM was shown to be correlated with smoking habits (p<0.01).Conclusions:The ELM-2 neoepitope was related to AMI whereas the ELM neoepitope was related to pulmonary diseases. These results indicate that elastin neoepitopes generated by the same proteases but at different amino acid sites provide different tissue-related information depending on the disease in question.

Original language	English
Article number	e60936
Journal	PLOS ONE
Volume	8
Issue number	6
Pages (from-to)	1-11
Number of pages	11
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0060936
Publication status	Published - 21 Jun 2013

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Skjøt-Arkil, H., Clausen, R. E., Rasmussen, L. M., Wang, W., Wang, Y., Zheng, Q., Mickley, H., Saaby, L., Diederichsen, A. C. P., Lambrechtsen, J., Martinez, F. J., Hogaboam, C. M., Han, M., Larsen, M. R., Nawrocki, A., Vainer, B., Krustrup, D., Bjørling-Poulsen, M., Karsdal, M. A., & Leeming, D. J. (2013). Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs. PLOS ONE, 8(6), 1-11. [e60936]. https://doi.org/10.1371/journal.pone.0060936

Skjøt-Arkil, H, Clausen, RE, Rasmussen, LM, Wang, W, Wang, Y, Zheng, Q, Mickley, H, Saaby, L, Diederichsen, ACP, Lambrechtsen, J, Martinez, FJ, Hogaboam, CM, Han, M, Larsen, MR, Nawrocki, A, Vainer, B, Krustrup, D, Bjørling-Poulsen, M, Karsdal, MA & Leeming, DJ 2013, 'Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs', PLOS ONE, vol. 8, no. 6, e60936, pp. 1-11. https://doi.org/10.1371/journal.pone.0060936

@article{227f9b5403f94eb7ab29f36e5f62448e,

title = "Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs",

abstract = "Background:Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two different diseases and if these fragments have the potential of being diagnostic biomarkers.Methods:Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope) generated at the amino acid position '552 in elastin by matrix metalloproteinase (MMP) -9/-12. A newly identified ELM neoepitope was generated by the same proteases but at amino acid position '441. The distribution of ELM-2 and ELM, in human arterial plaques and fibrotic lung tissues were investigated by immunohistochemistry. A competitive ELISA for ELM-2 was developed. The clinical relevance of the ELM and ELM-2 ELISAs was evaluated in patients with acute myocardial infarction (AMI), no AMI, high coronary calcium, or low coronary calcium. The serological release of ELM-2 in patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF) was compared to controls.Results:ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p<0.01). Levels of ELM were not significantly increased in these patients and no correlation was observed between ELM-2 and ELM. ELM-2 was not elevated in the COPD and IPF patients and was not correlated to ELM. ELM was shown to be correlated with smoking habits (p<0.01).Conclusions:The ELM-2 neoepitope was related to AMI whereas the ELM neoepitope was related to pulmonary diseases. These results indicate that elastin neoepitopes generated by the same proteases but at different amino acid sites provide different tissue-related information depending on the disease in question.",

author = "Helene Skj{\o}t-Arkil and Clausen, {Rikke E} and Rasmussen, {Lars M} and Wanchun Wang and Yaguo Wang and Qinlong Zheng and Hans Mickley and Lotte Saaby and Diederichsen, {Axel C P} and Jess Lambrechtsen and Martinez, {Fernando J} and Hogaboam, {Cory M} and Meilan Han and Larsen, {Martin R} and Arkadiusz Nawrocki and Ben Vainer and Dorrit Krustrup and Marina Bj{\o}rling-Poulsen and Karsdal, {Morten A} and Leeming, {Diana J}",

year = "2013",

month = jun,

day = "21",

doi = "10.1371/journal.pone.0060936",

language = "English",

volume = "8",

pages = "1--11",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "6",

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TY - JOUR

T1 - Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

AU - Skjøt-Arkil, Helene

AU - Clausen, Rikke E

AU - Rasmussen, Lars M

AU - Wang, Wanchun

AU - Wang, Yaguo

AU - Zheng, Qinlong

AU - Mickley, Hans

AU - Saaby, Lotte

AU - Diederichsen, Axel C P

AU - Lambrechtsen, Jess

AU - Martinez, Fernando J

AU - Hogaboam, Cory M

AU - Han, Meilan

AU - Larsen, Martin R

AU - Nawrocki, Arkadiusz

AU - Vainer, Ben

AU - Krustrup, Dorrit

AU - Bjørling-Poulsen, Marina

AU - Karsdal, Morten A

AU - Leeming, Diana J

PY - 2013/6/21

Y1 - 2013/6/21

N2 - Background:Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two different diseases and if these fragments have the potential of being diagnostic biomarkers.Methods:Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope) generated at the amino acid position '552 in elastin by matrix metalloproteinase (MMP) -9/-12. A newly identified ELM neoepitope was generated by the same proteases but at amino acid position '441. The distribution of ELM-2 and ELM, in human arterial plaques and fibrotic lung tissues were investigated by immunohistochemistry. A competitive ELISA for ELM-2 was developed. The clinical relevance of the ELM and ELM-2 ELISAs was evaluated in patients with acute myocardial infarction (AMI), no AMI, high coronary calcium, or low coronary calcium. The serological release of ELM-2 in patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF) was compared to controls.Results:ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p<0.01). Levels of ELM were not significantly increased in these patients and no correlation was observed between ELM-2 and ELM. ELM-2 was not elevated in the COPD and IPF patients and was not correlated to ELM. ELM was shown to be correlated with smoking habits (p<0.01).Conclusions:The ELM-2 neoepitope was related to AMI whereas the ELM neoepitope was related to pulmonary diseases. These results indicate that elastin neoepitopes generated by the same proteases but at different amino acid sites provide different tissue-related information depending on the disease in question.

AB - Background:Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated to two different diseases and if these fragments have the potential of being diagnostic biomarkers.Methods:Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope) generated at the amino acid position '552 in elastin by matrix metalloproteinase (MMP) -9/-12. A newly identified ELM neoepitope was generated by the same proteases but at amino acid position '441. The distribution of ELM-2 and ELM, in human arterial plaques and fibrotic lung tissues were investigated by immunohistochemistry. A competitive ELISA for ELM-2 was developed. The clinical relevance of the ELM and ELM-2 ELISAs was evaluated in patients with acute myocardial infarction (AMI), no AMI, high coronary calcium, or low coronary calcium. The serological release of ELM-2 in patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF) was compared to controls.Results:ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p<0.01). Levels of ELM were not significantly increased in these patients and no correlation was observed between ELM-2 and ELM. ELM-2 was not elevated in the COPD and IPF patients and was not correlated to ELM. ELM was shown to be correlated with smoking habits (p<0.01).Conclusions:The ELM-2 neoepitope was related to AMI whereas the ELM neoepitope was related to pulmonary diseases. These results indicate that elastin neoepitopes generated by the same proteases but at different amino acid sites provide different tissue-related information depending on the disease in question.

U2 - 10.1371/journal.pone.0060936

DO - 10.1371/journal.pone.0060936

M3 - Journal article

C2 - 23805173

SN - 1932-6203

VL - 8

SP - 1

EP - 11

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 6

M1 - e60936

ER -

Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

Abstract

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