Dipeptidyl peptidase-4 is increased in the abdominal aortic aneurysm vessel wall and is associated with aneurysm disease processes


Autoři: Moritz Lindquist Liljeqvist aff001;  Linnea Eriksson aff001;  Christina Villard aff001;  Mariette Lengquist aff001;  Malin Kronqvist aff001;  Rebecka Hultgren aff001;  Joy Roy aff001
Působiště autorů: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden aff001;  Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227889

Souhrn

Background

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease, and until today there is no other treatment available than surgical intervention. Dipeptidyl peptidase-4 (DPP4)-inhibitors, used clinically to treat type 2 diabetes, have in murine models been shown to attenuate aneurysm formation and decrease aortic wall matrix degradation, inflammation and apoptosis. Our aim was to investigate if DPP4 is present, active and differentially expressed in human AAA.

Methods and results

DPP4 gene expression was elevated in both media and adventitia of AAA tissue compared with control tissue, as measured by microarrays and qPCR, with consistent findings in external data. The plasma activity of DPP4 was however lower in male patients with AAA compared with age- and gender-matched controls, independently of comorbidity or medication. Immunohistochemical double staining revealed co-localization of DPP4 with cells positive for CD68, CD4 and -8, CD20, and SMA. Gene set enrichment analysis demonstrated that expression of DPP4 in AAA tissue correlated with expression of biological processes related to B- and T-cells, extracellular matrix turnover, peptidase activity, oxidative stress and angiogenesis whereas it correlated negatively with muscle-/actin-related processes.

Conclusion

DPP4 is upregulated in both media and adventitia of human AAA and correlates with aneurysm pathophysiological processes. These results support previous murine mechanistic studies and implicate DPP4 as a target in AAA disease.

Klíčová slova:

Aneurysms – Aorta – Blood plasma – Diabetes mellitus – Gene expression – Inflammatory diseases – Macrophages – Microarrays


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