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 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 elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects

Arterial stiffening may be linked to the reduced bioactivity of nitric oxide (NO) and increased plasma concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA). The aim of this study was to investigate whether large (C1) and small artery (C2) elasticity is associated with endothelial function index (EFI) and plasma concentration of ADMA. We included 63 healthy subjects, aged 19 to 70 years, in the study. EFI, C1 and C2 were assessed by pulse wave analysis (PWA) and ADMA level was measured using an enzyme‐linked immunoassay. Linear regression analysis revealed significant positive correlation between EFI and both C1 and C2 (R = 0.29, p = 0.02; R = 0.38, p = 0.002, respectively). A significant inverse association occurred between ADMA and C1 as well as C2 (R = ?0.32, p = 0.03; R = ?0.37, p = 0.009, respectively). In multiple regression analysis, C2 was determined by EFI, ADMA, age and BMI, and C1 was correlated with EFI, age and BMI. These findings suggest that endothelial vasodilatory dysfunction and accumulation of ADMA may be important mechanisms underlying reduced arterial elasticity in healthy subjects.     

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.     

Whole-exome sequencing identifies a potential TTN mutation in a multiplex family with inguinal hernia

Hernia - Inguinal hernia repair is one of the most common procedures in general surgery. Males are seven times more likely than females to develop a hernia and have a 27&nbsp;% lifetime...     

Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated hearts

Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia-reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose-response to phenylephrine (PHE), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 +/- 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 +/- 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.     

Genotype-first approach to the detection of hereditary breast and ovarian cancer risk,and effects of risk disclosure to biobank participants

Genotype-first approach allows to systematically identify carriers of pathogenic variants in BRCA1/2 genes conferring a high risk of familial breast and ovarian cancer. Participants of the Estonian biobank have expressed support for the disclosure of clinically significant findings. With an Estonian biobank cohort, we applied a genotype-first approach, contacted carriers, and offered return of results with genetic counseling. We evaluated participants’ responses to and the clinical utility of the reporting of actionable genetic findings. Twenty-two of 40 contacted carriers of 17 pathogenic BRCA1/2 variants responded and chose to receive results. Eight of these 22 participants qualified for high-risk assessment based on National Comprehensive Cancer Network criteria. Twenty of 21 counseled participants appreciated being contacted. Relatives of 10 participants underwent cascade screening. Five of 16 eligible female BRCA1/2 variant carriers chose to undergo risk-reducing surgery, and 10 adhered to surveillance recommendations over the 30-month follow-up period. We recommend the return of results to population-based biobank participants; this approach could be viewed as a model for population-wide genetic testing. The genotype-first approach permits the identification of individuals at high risk who would not be identified by application of an approach based on personal and family histories only.Subject terms: Genetic counselling, Population screening, Cancer genomics     

Population-based type-specific prevalence of high-risk human papillomavirus infection in Estonia

Background  

Effective prophylactic vaccines are available against human papillomavirus (HPV) types 6, 11, 16, and 18 which are licensed for routine use among young women. Monitoring is needed to demonstrate protection against cervical cancer, to verify duration of protection, and assess replacement frequency of non-vaccine types among vaccinated cohorts.