Skjøt-Arkil, Helene2; Clausen, Rikke E3; Rasmussen, Lars M3; Wang, Wanchun3; Wang, Yaguo3; Zheng, Qinlong3; Mickley, Hans3; Saaby, Lotte3; Diederichsen, Axel C P3; Lambrechtsen, Jess3; Martinez, Fernando J3; Hogaboam, Cory M3; Han, Meilan3; Larsen, Martin R3; Nawrocki, Arkadiusz3; Vainer, Ben6; Krustrup, Dorrit7; Bjørling-Poulsen, Marina3; Karsdal, Morten A3; Leeming, Diana J3
1 Section of Molecular Pathology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 Nordic Bioscience A/S, Herlev, Denmark ; School of Endocrinology, University of Southern Denmark, Odense, Denmark.3 unknown4 Issazadeh-Navikas Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet6 Issazadeh-Navikas Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet7 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
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.