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

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 F2a (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.

Antioxidant UPF1 attenuates myocardial stunning in isolated rat hearts.

Oxidative stress is a crucial pathophysiological mechanism of myocardial ischaemia-reperfusion injury (IRI). We evaluated the cardioprotective effects of a novel glutathione analogue, UPF1 (4-methoxy-L-tyrosinyl-gamma-L-glutamyl-L-cysteinyl-glycine; MW 483.5), on an isolated rat heart model of thirty-minute global ischaemia followed by 90 min of reperfusion. Treatment with UPF1 (1 mg/ml) prior to ischaemia improved the recovery of post-ischaemic left ventricular end-diastolic pressure (p=0.046), developed pressure (p=0.002) and coronary flow (p=0.01). No protective effect was observed when the hearts were treated with UPF1 after ischaemia. Administration of UPF1 had no influence upon infarct size or enzyme leakage from the heart. The results suggest that glutathione analogue type of biomolecules could possess a therapeutic potential in clinical situations where myocardial IRI is presented as myocardial stunning rather than tissue infarction.

Impact of oxidative stress on arterial elasticity in patients with atherosclerosis.

BACKGROUND: Alterations in the elastic behavior of arteries is an early sign of vascular damage in atherogenesis and may be promoted by oxidative stress (OxS). However, studies designed for simultaneous assessment of arterial elasticity and OxS status in patients with peripheral arterial disease (PAD) are absent. The purpose of this study was to assess large (C1) and small artery elasticity (C2) and indices of OxS in patients with PAD as well as to investigate possible relationships between these parameters. METHODS: Arterial elasticity was assessed noninvasively by pulse wave analysis (PWA) and biochemical measurements were taken from 38 patients with PAD and from 28 matched control subjects. The elasticity indices of the arteries were derived from PWA based on the modified Windkessel model and the OxS status was measured using urinary 8-iso-prostaglandin F2alpha (F2-IsoPs) and plasma baseline diene conjugates of low-density lipoproteins (LDL-BDC). RESULTS: Patients with PAD showed significantly reduced C1 and C2 and increased values of F2-IsoPs and LDL-BDC. There was an inverse association between C1 and F2-IsoPs, as well as between C2 and F2-IsoPs (R=-.3, P=.04; R=-.49, P=.002, respectively) in the patient group, but not in the controls. After controlling for potential confounders in a multiple regression model, the associations between C2 and F2-IsoPs remained significant in the patient group (P<.001). CONCLUSIONS: The possible link between arterial elasticity and F2-IsoPs in patients with PAD suggests that oxidative modifications may be involved in alterations of arterial elastic properties in atherosclerosis.

Effects of stimulation of nitric oxide synthesis on large artery stiffness in patients with peripheral arterial disease.

The role of endothelium-derived nitric oxide (NO) in modulation of large artery stiffness in patients with peripheral arterial disease (PAD) is unexplored. The aim of this study was to evaluate, using pulse wave analysis (PWA), changes in aortic and systemic arterial stiffness following administration of nitroglycerin and beta(2)-agonist salbutamol in PAD patients (n = 24) and in healthy controls (n = 24). Changes in estimated aortic pulse wave velocity (T(r)) and in augmentation index (AIx), following administration of nitroglycerin and salbutamol, were assessed using PWA. Salbutamol-induced changes in T(r) and in AIx were significantly reduced in PAD patients (P < 0.001 and < 0.001, respectively), while nitroglycerin-produced changes were not different (P = 0.25 and 0.35, respectively). Changes in T(r) after salbutamol administration were independent of changes in mean arterial pressure (MAP) (R = -0.21, P = 0.16). This study shows that stimulation of NO synthesis fails to modify stiffness of the large arteries in PAD patients and changes in aortic stiffness are independent of changes in MAP. Our data support the utility of PWA as a non-invasive method for assessment of NO-mediated vascular changes.