Chemokine Receptor 2 Is A Theranostic Biomarker for Abdominal Aortic Aneurysms

作者：Santiago Elizondo-Benedetto, Sergio Sastriques-Dunlop, Lisa Detering, Batool Arif, Gyu Seong Heo, Deborah Sultan, Hannah Luehmann, Xiaohui Zhang, Xuefeng Gao, Kitty Harrison, Dakkota Thies, Laura McDonald, Christophe Combadière, Chieh‐Yu Lin, Yeona Kang, Jie Zheng, Joseph E. Ippolito, Richard Laforest, Robert J. Gropler, Sean J. English, Mohamed A. Zayed, Yongjian Liu · 发表于：medRxiv · 年份：2023 · DOI：10.1101/2023.11.06.23298031 · 被引用次数：6 · 研究领域：Aortic aneurysm repair treatments、Abdominal vascular conditions and treatments、Aortic Disease and Treatment Approaches

Abstract Abdominal aortic aneurysm (AAA) is a degenerative vascular disease impacting aging populations with a high mortality upon rupture. There are no effective medical therapies to prevent AAA expansion and rupture. We previously demonstrated the role of the monocyte chemoattractant protein-1 (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis in rodent AAA pathogenesis via positron emission tomography/computed tomography (PET/CT) using CCR2 targeted radiotracer 64 Cu-DOTA-ECL1i. We have since translated this radiotracer into patients with AAA. CCR2 PET showed intense radiotracer uptake along the AAA wall in patients while little signal was observed in healthy volunteers. AAA tissues collected from individuals scanned with 64 Cu-DOTA-ECL1i and underwent open-repair later demonstrated more abundant CCR2+ cells compared to non-diseased aortas. We then used a CCR2 inhibitor (CCR2i) as targeted therapy in our established male and female rat AAA rupture models. We observed that CCR2i completely prevented AAA rupture in male rats and significantly decreased rupture rate in female AAA rats. PET/CT revealed substantial reduction of 64 Cu-DOTA-ECL1i uptake following CCR2i treatment in both rat models. Characterization of AAA tissues demonstrated decreased expression of CCR2+ cells and improved histopathological features. Taken together, our results indicate the potential of CCR2 as a theranostic biomarker for AAA management. Graphical Abstract