PMID- 37986880
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2023 Nov 7
TI  - Chemokine Receptor 2 Is A Theranostic Biomarker for Abdominal Aortic Aneurysms.
LID - 2023.11.06.23298031 [pii]
LID - 10.1101/2023.11.06.23298031 [doi]
AB  - 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.
FAU - Elizondo-Benedetto, Santiago
AU  - Elizondo-Benedetto S
FAU - Sastriques-Dunlop, Sergio
AU  - Sastriques-Dunlop S
FAU - Detering, Lisa
AU  - Detering L
FAU - Arif, Batool
AU  - Arif B
FAU - Heo, Gyu Seong
AU  - Heo GS
FAU - Sultan, Deborah
AU  - Sultan D
FAU - Luehmann, Hannah
AU  - Luehmann H
FAU - Zhang, Xiaohui
AU  - Zhang X
AUID- ORCID: 0000-0002-4927-2117
FAU - Gao, Xuefeng
AU  - Gao X
FAU - Harrison, Kitty
AU  - Harrison K
FAU - Thies, Dakkota
AU  - Thies D
FAU - McDonald, Laura
AU  - McDonald L
FAU - Combadiere, Christophe
AU  - Combadiere C
FAU - Lin, Chieh-Yu
AU  - Lin CY
FAU - Kang, Yeona
AU  - Kang Y
FAU - Zheng, Jie
AU  - Zheng J
FAU - Ippolito, Joseph
AU  - Ippolito J
AUID- ORCID: 0000-0003-1913-5573
FAU - Laforest, Richard
AU  - Laforest R
FAU - Gropler, Robert J
AU  - Gropler RJ
FAU - English, Sean J
AU  - English SJ
FAU - Zayed, Mohamed A
AU  - Zayed MA
FAU - Liu, Yongjian
AU  - Liu Y
AUID- ORCID: 0000-0002-1118-1535
LA  - eng
GR  - S10 OD025214/OD/NIH HHS/United States
PT  - Preprint
DEP - 20231107
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
PMC - PMC10659515
EDAT- 2023/11/21 06:42
MHDA- 2023/11/21 06:43
PMCR- 2023/11/20
CRDT- 2023/11/21 05:08
PHST- 2023/11/21 06:43 [medline]
PHST- 2023/11/21 06:42 [pubmed]
PHST- 2023/11/21 05:08 [entrez]
PHST- 2023/11/20 00:00 [pmc-release]
AID - 2023.11.06.23298031 [pii]
AID - 10.1101/2023.11.06.23298031 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2023 Nov 7:2023.11.06.23298031. doi: 
      10.1101/2023.11.06.23298031.