Targeting myeloperoxidase to stabilize unruptured aneurysm: an imaging-guided approach.

Autor: Shi X; Medical Imaging Key Laboratory of Sichuan province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China.; Department of Cardiovascular disease, School of Clinical Medicine, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China., Xue Y; Medical Imaging Key Laboratory of Sichuan province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China.; Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Fujiang Road 234, Nanchong City, 637000, Sichuan, China., Wu H; Medical Imaging Key Laboratory of Sichuan province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China.; School of Pharmacy, North Sichuan Medical College, Fujiang Road 234, Nanchong City, 637000, Sichuan, China., Shen C; Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Fujiang Road 234, Nanchong City, 637000, Sichuan, China., Zhong L; Medical Imaging Key Laboratory of Sichuan province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China., Lei J; School of Pharmacy, North Sichuan Medical College, Fujiang Road 234, Nanchong City, 637000, Sichuan, China., Xia Z; Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Fujiang Road 234, Nanchong City, 637000, Sichuan, China. Xiazhiyang@nsmc.edu.cn., Yang Y; Medical Imaging Key Laboratory of Sichuan province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China. yangying@nsmc.edu.cn.; Department of Cardiovascular disease, School of Clinical Medicine, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China. yangying@nsmc.edu.cn., Zhu J; Medical Imaging Key Laboratory of Sichuan province, Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Maoyuan Road 1, Nanchong City, 637000, Sichuan, China. zhujiang@nsmc.edu.cn.; School of Pharmacy, North Sichuan Medical College, Fujiang Road 234, Nanchong City, 637000, Sichuan, China. zhujiang@nsmc.edu.cn.
Jazyk: angličtina
Zdroj: BMC cardiovascular disorders [BMC Cardiovasc Disord] 2024 Mar 20; Vol. 24 (1), pp. 169. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1186/s12872-024-03822-1
Abstrakt: Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and - 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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