Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis

Abstract

Inflammation and oxidative stress (OxS) play key roles in atherogenesis; however, their causal relationship is not yet completely understood. Much attention has been given to the possibility that inflammation is a primary process of atherosclerosis and that OxS may be a by‐product of the inflammatory process. We hypothesized, accordingly, that chronic systemic inflammation affects endothelial vasomotor function in the subclinical condition, whereas oxidative modifications are more involved in the structural stiffening of the arteries in atherosclerosis. The aim of our study was to test this hypothesis. Endothelial function and arterial stiffness were assessed non‐invasively by pulse wave analysis, and blood/urinary samples were taken in 39 patients with peripheral arterial disease as well as in 34 controls. The patients showed significantly reduced endothelial function index (EFI) and increased augmentation index (AIx), as well as higher estimated aortic pulse wave velocity (PWV) and elevated values of the intercellular adhesion molecule‐1 (ICAM‐1), high sensitivity C‐reactive protein, myeloperoxidase and urinary 8‐iso‐prostaglandin F_2a (F₂‐IsoPs). There was an inverse association between EFI and ICAM‐1 (R = −0.44, p = 0.009) in the controls, but not in the patients. Augmentation index and estimated aortic PWV correlated with F₂‐IsoPs only in the patients (R = 0.5, p = 0.001; R = −0.43, p = 0.006, respectively). After controlling for potential confounders, these associations remained significant. The study demonstrates that impairment of endothelial vasomotor capacity is affected by degree of inflammation in the subclinical condition, whereas arterial stiffening is determined by level of oxidative modifications in atherosclerosis.

• Arterial stiffness
• atherosclerosis
• endothelium
• inflammation
• oxidative stress

Acknowledgements

We are indebted to E. Jaigma for linguistic revision of the text and to Ü. Piirisild for technical assistance. The study was supported by grants from the Estonian Science Foundation (nos. 5833 and 6588) and by target financing (nos. 0182548As03 and PARBK 06906).