Gene expression of inflammasome components in peripheral blood mononuclear cells (PBMC) of vascular patients increases with age

Background: Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22–82) in association with age. Findings: Linear regression of real-time qRT-PCR data revealed a significant positive association of gene expression of each of the inflammasome components with age (Pearson correlation coefficients: AIM2: r = 0.245; P = 0.032; NLRP3: r = 0.367; P = 0.001; ASC (PYCARD): r = 0.252; P = 0.027; CASP1: r = 0.296; P = 0.009; CASP5: r = 0.453; P = 0.00003; IL1B: r = 0.247; P = 0.030). No difference in gene expression of AIM2, NLRP3, ASC CASP1, and CASP5 was detected between PBMC of patients with advanced atherosclerosis and other vascular patients, whereas IL1B expression was increased in PBMC of the latter group (P = 0.0005). Conclusion: The findings reinforce the systemic pro-inflammatory phenotype reported in elderly by demonstrating an increased phase-1 activation of inflammasomes in PBMC of vascular patients

Altered in-stent hemodynamics may cause erroneous upgrading of moderate carotid artery restenosis when evaluated by duplex ultrasound

ObjectiveTo assess the influence of stent application on in-stent hemodynamics under standardized conditions.MethodsOvine common carotid arteries before and after stent (6 × 40 mm, sinus-Carotid-RXt, combined open-closed cell design; Optimed, Ettlingen, Germany) application were used. Plastic tubes, 10 mm in length, simulating stenosis were placed in the middle of the applied stent to induce different degrees of stenosis (moderate 57.8% and severe 76.4%). Flow velocity and dynamic compliance were, respectively, measured with ultrasound and laser scan; proximal, in-stent, and distal to the stented arterial segment (1 cm proximal and distal) in a pulsatile ex vivo circulation system.ResultsStent insertion caused the in-stent peak systolic velocity to increase 22% without stenosis, 31% with moderate stenosis, and 23% with severe stenosis. Stent insertion without stenosis caused no significant increase in in-stent end-diastolic velocity (EDV) but a 17% increase with moderate stenosis. In severe stenosis, EDV was increased 56% proximal to the stenosis. Compliance was reduced threefold in the middle of the stented arterial segment where flow velocity was significantly increased.ConclusionsWith or without stenosis, stent introduction caused the in-stent peak systolic velocity to become significantly elevated compared with a nonstented area. EDV was also increased by stent insertion in the case of moderate stenosis. The stent-induced compliance reduction may be causal for the increase in flow velocity since the stent-induced flow velocity elevation appeared in the stented area with low compliance. Because of altered hemodynamics caused by stent introduction when measured by duplex ultrasound, caution is prudent in concluding that carotid artery stenting is associated with a higher restenosis rate than carotid endarterectomy. Mistakenly upgrading moderate to severe restenosis could result in unnecessary reintervention.Clinical RelevanceClinical experience and prior studies support the supposition that restenosis after carotid artery stenting in carotid lesions displays erroneously elevated velocity when evaluated by duplex ultrasound (DUS), thus contributing to misleading interpretation of the degree of stenosis. This study, in contrast to studies of other groups, employs exactly the same conditions to measure flow with DUS in an unstented and then stented section of the carotid artery. Since DUS is the first-choice tool for carotid artery evaluation, knowledge about inexactness of the method is essential to avoid errors in treatment or follow-up decisions

Arterial Aneurysm Localization Is Sex-Dependent

The aim of this study was to investigate sex-dependent aneurysm distributions. A total of 3107 patients with arterial aneurysms were diagnosed from 2006 to 2016. Patients with anything other than true aneurysms, hereditary connective tissue disorders or vasculitides (n = 918) were excluded. Affected arterial sites and age at first aneurysm diagnosis were compared between women and men by an unpaired two-tailed t-test and Fisher’s exact test. The study sample consisted of 2189 patients, of whom 1873 were men (85.6%) and 316 women (14.4%) (ratio m:w = 5.9:1). Men had considerably more aneurysms in the abdominal aorta (83.4% vs. 71.1%; p p p p p p p p < 0.001). Age at disease onset and further aneurysm distribution showed no considerable difference. The infrarenal segment might be considered a natural border for aneurysm formation in men and women suspected to have distinct genetic, pathophysiologic and ontogenetic factors. Screening modalities for women at risk might need further adjustment, particularly thoracic cross-sectional imaging complementation

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

Abstract Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients

Single-center experience in the management of spontaneous isolated abdominal aortic dissection

OBJECTIVE This study aims to report the management of patients with spontaneous isolated dissection of the abdominal aorta (sIAAD). METHODS A cohort of 18 consecutive patients (12 male, mean age 58 years) with sIAAD was treated between 1990 and 2009. Dissection was asymptomatic in ten and symptomatic in eight patients. Retrospective data analysis from patient charts was performed. Follow-up included clinical examination, ultrasound, and/or CT-angiography. Mean follow-up was 54 months (range 1-211). RESULTS In total, eight out of 18 received invasive treatment. All asymptomatic patients initially underwent conservative treatment and surveillance. Spontaneous false lumen thrombosis occurred in four (40 %), and three patients showed relevant aneurysmatic progression and underwent elective invasive treatment (open n = 2, endovascular n = 1), representing a crossover rate of 30 %. Late mortality was 20 % (n = 2) in this group. In symptomatic patients, five underwent urgent treatment due to persistent abdominal or back pain (n = 4) or contained rupture (n = 1); one was treated for claudication. The remaining two patients presented with irreversible spinal cord ischemia and were treated conservatively. Three patients were treated by open surgery and three by endovascular interventions (two stentgrafts, one Palmaz XXL stent). Early and late morbidity and mortality was 0 % in this group. There were no reinterventions CONCLUSION: The majority of patients with sIADD require invasive treatment, with EVAR being the preferable treatment option today. In asymptomatic IADD, primary surveillance is justifiable, but close surveillance due to expansion is necessary

Additional file 2: of Gene expression of inflammasome components in peripheral blood mononuclear cells (PBMC) of vascular patients increases with age

Materials and methods. (DOCX 24 kb