Myeloid related protein 8/14 is a new candidate biomarker and therapeutic target for abdominal aortic aneurysm.

Abstract

Open surgical or percutaneous endovascular (EVAR) intervention is the only approved treatment for abdominal aortic aneurysm (AAA). Novel targeted therapy and companion diagnostic are needed. Our study aimed to investigate the expression of myeloid related protein 8/14 (MRP8/14) in AAA and explore whether MRP8/14 can be a biomarker and therapeutic target for AAA. The serum levels of MRP8/14 and inflammatory factors including TNF-α, IL-1β, and IL-6 were increased in 20 human AAA patients compared to healthy people by ELISA assay. The mRNA and protein expressions of MRPs in AAA tissues of AAA patient were significantly elevated when compared with the levels in adjacent non-aneurysmal aortic segments in AAA patients. through PCR and western blot analysis. Correlation analysis and receiver operating characteristic (ROC) curve analysis confirmed that MRP8/14 was secreted into the serum and possessed the potential diagnostic value. Rat AAA models established by perfusion porcine pancreatic elastase and murine macrophage RAW264.7 cells were used to evaluate the mechanisms of MRP8/14 after treatment with antibodies. Similarly, MRP8, MRP14, and MRP8/14 were highly expressed in rat AAA model, while the administrations of antibodies of MRPs significantly reversed the improvement expressions of MRP8 and MRP14. In RAW264.7 cells, MRPs especially for MRP8/14 obviously increased the levels of MMP-2 and MMP-9. Under MRP8/14 stimulation, the antibodies of MRPs recovered the expressions of MMP-2 and MMP-9. Anti MRP8/14 antibody exhibited the strongest effect in the experiments. Our results indicated that MRP8/14 was associated with AAA presence and progression and could be considered as a biomarker for AAA diagnose. Anti MRP8/14 can be a potential therapeutic target for treatment of AAA.

• Authors: Peng Liu, Ziqiang Sun, Yanhui Zhang, Wei Guo
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 118 Pg. 109229 (Oct 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 31351425 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Masson SAS.

Chemical References

• Biomarkers
• Leukocyte L1 Antigen Complex
• RNA, Messenger
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Adult
• Animals
• Aortic Aneurysm, Abdominal (blood, metabolism, therapy)
• Biomarkers (metabolism)
• Disease Models, Animal
• Female
• Humans
• Leukocyte L1 Antigen Complex (blood, genetics, metabolism)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Middle Aged
• Models, Biological
• Molecular Targeted Therapy
• RAW 264.7 Cells
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Swine