Phenotypic characterization of circulating endothelial cells induced by inflammation and oxidative stress in ankylosing spondylitis

Abstract

Ankylosing spondylitis (AS) is a chronic auto-immune disease, affecting the spine, sacroiliac, and sometimes peripheral joints. It is also involved with cardio-vascular risk factors due to accelerated atherosclerosis. Oxidative burst, systemic inflammation coupled with endothelial dysfunction (ED), resulting in reduced bioavailability of the vasodilator nitric oxide (NO) and an increased number of circulating endothelial cells (CECs) may correlate with disease activity and its sustenance. Hence, the study was aimed to detect and quantify CECs and assess the oxidative stress and inflammatory status in AS patients vis-à-vis healthy controls, as well as relate these parameters with AS disease activity and atherosclerotic markers in patients. Our study showed an increased frequency of endothelial cells in peripheral blood of AS patients in pro-inflammatory conditions. In AS patient population, they showed significant reduction of flow-mediated dilatation (%FMD) (p < 0.05), and increased soluble adhesion molecules such as sICAM-1 (p < 0.01) and sVCAM-1 (p < 0.05) compared to healthy controls. A marked increase in pro-inflammatory markers such as TNF-α (p < 0.01) and IL-1β (p < 0.001) and reactive free radicals (p < 0.05) along with reduced serum nitrite in AS, provided a strong pro-inflammatory milieu which positively correlated with Bath ankylosing spondylitis disease activity and functional indices (BASDAI and BASFI). The observed significant upregulation in CECs (CD45^-/CD31⁺/CD105⁺/CD144⁺) in patients compared to healthy controls positively correlated with disease activity and duration as well as with markers of oxidative stress. Thus, chronic inflammation and oxidative burst induce loss of NO bioavailability, leading to ED. This may cause the derangement of CECs that may be considered as a prognostic biomarker for ED.

Keywords:

• Cell adhesion
• circulating endothelial cells
• endothelial dysfunction
• nitric oxide
• oxidative stress

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by funding from the Board of Research in Nuclear Sciences, BRNS (Bhabha Atomic Research Centre, BARC, Mumbai), Govt. of India, Dept. of Atomic Energy, 37(1)/14/12/2016-BRNS/37026. We are grateful to the "Establishment of Multidisciplinary Research Unit" no: V.25011/103/2016-HR, Dept. of Health Research, Govt. of India for extending their help.