C-C Chemokine Receptor 2 is a Tissue Biomarker for Abdominal Aortic Aneurysmal and Occlusive Disease.

Abstract

This study evaluated whether C-C Chemokine Receptor 2 (CCR2) is a tissue biomarker of aortic disease severity, particularly in patients with abdominal aortic aneurysm (AAA). There is an unmet clinical need for tissue biomarkers that can monitor AAA progression and predict rupture risk. Given the key role of inflammation in AAA pathogenesis, we hypothesized that CCR2, involved in the recruitment and activation of immune cells, is upregulated in AAAs. We used our human vascular biobank to obtain aortic tissue from 42 individuals with non-ruptured and ruptured AAA (rAAA), aortoiliac occlusive disease (AOD), or normal abdominal aorta (NAA). We evaluated aortic wall CCR2-positive cellular content and aortic tissue levels of cytokines and CCR2 ligand, monocyte chemoattractant protein 1 (MCP1). Additionally, a single-cell RNA sequencing dataset was analyzed to assess Ccr2 expression in human AAA tissues. Compared with NAA, the aneurysmal aorta (AAA and rAAA) demonstrated significantly higher CCR2-positive cellular content (P<0.05). The number of aortic wall CCR2-positive macrophages was significantly elevated in individuals with AAA (P<0.05), rAAA (P<0.01), and AOD (P<0.01). We also observed higher levels of MCP1 and inflammatory cytokines in diseased aortic tissue. Furthermore, single-cell transcriptomics revealed that in AAA tissue, Ccr2 is predominantly expressed by macrophages (69%), followed by T-cells (22%), and B-cells (8%). Our findings indicate that CCR2 is a promising biomarker for diseased aortic tissue, particularly in the setting of AAA. These findings suggest potential applications for novel molecular imaging and pharmacological targeting.