TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2)
Background and aims: TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular p...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Atherosclerosis Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667089522000505 |
| _version_ | 1811187839370526720 |
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| author | Melody Chemaly Roisin McAllister Aaron Peace Anthony John Bjourson Steve Watterson Andrew Parton Matthias Clauss Victoria McGilligan |
| author_facet | Melody Chemaly Roisin McAllister Aaron Peace Anthony John Bjourson Steve Watterson Andrew Parton Matthias Clauss Victoria McGilligan |
| author_sort | Melody Chemaly |
| collection | DOAJ |
| description | Background and aims: TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular pathway with potential for acute coronary syndrome (ACS) and major adverse cardiovascular events (MACE) prediction. Methods: Blood samples were obtained from consecutive patients (n = 229) with coronary angiographic evidence of CAD admitted with ACS or electively. MACE were recorded after a median 3-year follow-up. Controls (n = 115) had a <10% CAD risk as per the HeartSCORE. TACE and TIMP3 protein and mRNA levels were measured by ELISA and RT-qPCR respectively. TACE substrates were measured using a multiplex proximity extension assay. Results: TACE mRNA and cell protein levels (p < 0.01) and TACE substrates LDLR (p = 0.006), TRANCE (p = 0.045), LAG-3 (p < 0.001) and ACE2 (p < 0.001) plasma levels were significantly higher in CAD patients versus controls. TACE inhibitor TIMP3 mRNA levels were significantly lower in CAD patients and tended to be lower in the ACS population (p < 0.05). TACE substrates TNFR1 (OR:3.237,CI:1.514–6.923,p = 0.002), HB-EGF (OR:0.484,CI:0.288–0.813,p = 0.006) and Ep-CAM (OR:0.555,CI:0.327–0.829,p = 0.004) accurately classified ACS patients with HB-EGF and Ep-CAM levels being lower compared to electively admitted patients. TNFR1 (OR:2.317,CI:1.377–3.898,p = 0.002) and TNFR2 (OR:1.902,CI:1.072–3.373,p = 0.028) were significantly higher on admission in those patients who developed MACE within 3 years. Conclusions: We demonstrate a possible role of TACE substrates LAG-3, HB-EGF and Ep-CAM in atherosclerotic plaque development and stability. We also underline the importance of measuring TNFR1 and TNFR2 earlier than previously appreciated for MACE prediction. We report an important role of TIMP3 in regulating TACE levels. |
| first_indexed | 2024-04-11T14:09:17Z |
| format | Article |
| id | doaj.art-6d6960644a344e22bf53dc8481fe6cc7 |
| institution | Directory Open Access Journal |
| issn | 2667-0895 |
| language | English |
| last_indexed | 2024-04-11T14:09:17Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Atherosclerosis Plus |
| spelling | doaj.art-6d6960644a344e22bf53dc8481fe6cc72022-12-22T04:19:46ZengElsevierAtherosclerosis Plus2667-08952022-12-01504049TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2)Melody Chemaly0Roisin McAllister1Aaron Peace2Anthony John Bjourson3Steve Watterson4Andrew Parton5Matthias Clauss6Victoria McGilligan7Department of Molecular Medicine and Surgery, Karolinska Institute, SE-171 76 Solna, Sweden; Corresponding author.Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital, Londonderry, BT47 6SB, Northern Ireland, UKNorthern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital, Londonderry, BT47 6SB, Northern Ireland, UK; Cardiology Department, Western Health and Social Care Trust, Altnagelvin Hospital, Glenshane Road, Londonderry, BT47 6SB, Northern Ireland, UKNorthern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital, Londonderry, BT47 6SB, Northern Ireland, UKNorthern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital, Londonderry, BT47 6SB, Northern Ireland, UKEnsembl Variation, EMBL-EBI, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, UKDepartment of Cellular and Integrative Physiology, Indiana University, Indianapolis, IN, 46202, USA; Centre for Molecular Bioscience, Ulster University, Coleraine, BT52 1SA, Northern Ireland, UKNorthern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Altnagelvin Hospital, Londonderry, BT47 6SB, Northern Ireland, UKBackground and aims: TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular pathway with potential for acute coronary syndrome (ACS) and major adverse cardiovascular events (MACE) prediction. Methods: Blood samples were obtained from consecutive patients (n = 229) with coronary angiographic evidence of CAD admitted with ACS or electively. MACE were recorded after a median 3-year follow-up. Controls (n = 115) had a <10% CAD risk as per the HeartSCORE. TACE and TIMP3 protein and mRNA levels were measured by ELISA and RT-qPCR respectively. TACE substrates were measured using a multiplex proximity extension assay. Results: TACE mRNA and cell protein levels (p < 0.01) and TACE substrates LDLR (p = 0.006), TRANCE (p = 0.045), LAG-3 (p < 0.001) and ACE2 (p < 0.001) plasma levels were significantly higher in CAD patients versus controls. TACE inhibitor TIMP3 mRNA levels were significantly lower in CAD patients and tended to be lower in the ACS population (p < 0.05). TACE substrates TNFR1 (OR:3.237,CI:1.514–6.923,p = 0.002), HB-EGF (OR:0.484,CI:0.288–0.813,p = 0.006) and Ep-CAM (OR:0.555,CI:0.327–0.829,p = 0.004) accurately classified ACS patients with HB-EGF and Ep-CAM levels being lower compared to electively admitted patients. TNFR1 (OR:2.317,CI:1.377–3.898,p = 0.002) and TNFR2 (OR:1.902,CI:1.072–3.373,p = 0.028) were significantly higher on admission in those patients who developed MACE within 3 years. Conclusions: We demonstrate a possible role of TACE substrates LAG-3, HB-EGF and Ep-CAM in atherosclerotic plaque development and stability. We also underline the importance of measuring TNFR1 and TNFR2 earlier than previously appreciated for MACE prediction. We report an important role of TIMP3 in regulating TACE levels.http://www.sciencedirect.com/science/article/pii/S2667089522000505Coronary artery diseaseTumour necrosis factor alpha converting enzyme TACE/ADAM17Major adverse cardiovascular eventsAcute coronary syndrome |
| spellingShingle | Melody Chemaly Roisin McAllister Aaron Peace Anthony John Bjourson Steve Watterson Andrew Parton Matthias Clauss Victoria McGilligan TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) Atherosclerosis Plus Coronary artery disease Tumour necrosis factor alpha converting enzyme TACE/ADAM17 Major adverse cardiovascular events Acute coronary syndrome |
| title | TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) |
| title_full | TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) |
| title_fullStr | TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) |
| title_full_unstemmed | TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) |
| title_short | TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2) |
| title_sort | tace adam17 substrates associate with acs ep cam hb egf and follow up mace tnfr1 and tnfr2 |
| topic | Coronary artery disease Tumour necrosis factor alpha converting enzyme TACE/ADAM17 Major adverse cardiovascular events Acute coronary syndrome |
| url | http://www.sciencedirect.com/science/article/pii/S2667089522000505 |
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