Complement C5 plasma levels are associated to abdominal aortic aneurysm prevalence and progression

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Complemento II-CM La Caixa Aim Previous human and experimental studies have suggested a role of complement activation in abdominal aortic aneurysm (AAA). We recently described an increase in complement C5 levels in plasma of subjects with subclinical atherosclerosis (1). Our aim was to investigate the potential association of C5 with AAA presence and progression. Material and methods Tissue and tissue-conditioned media from AAA (thrombus and wall) or healthy samples were obtained from surgical repair or brain-deceased organ donors, respectively. Blood samples from 490 AAA patients (maximal aortic diameter ≥30 mm) were obtained within a population-based ultrasound-screening trial in Danish men and from 176 age-matched screened negative controls. C5 protein levels were assessed by immunohistochemistry and ELISA. Results High C5 positive immunostaining was observed in AAA thrombus and media, while the staining in healthy arteries was faint. C5 levels were higher in tissue-conditioned media from AAA thrombus and AAA media as compared to healthy arteries (7.1±1 vs 2.9 ±0.5 vs 1.2±0.2ug/ml, p<0.0001 for both). C5 plasma levels in AAA patients were higher than in controls (116±8 vs 61±7 ug/ml, P<0.001). AAA patients at the upper tertile of C5 at baseline had a 25% higher risk of needing surgical repair during the follow-up (Hazard Ratio=1.25, 95% confidence interval, 1.045;1.511, P<0.05). Conclusions C5 is associated to AAA presence and progression suggesting its potential use as a prognostic marker. Future studies are needed to clarify the pathogenic role of C5 in AAA.