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Background Ischemia/reperfusion (I/R) injury represents one of the most severe complications in vascular surgery where cross-clamping of the aorta and subsequent visceral ischemia are a recurrent issue. The literature describes a family of nuclear receptors, that is, peroxisome proliferator–activated receptors (PPARs), in particular PPARγ isoform, which are important modulators of vascular inflammation resulting from I/R injury. The aim of our study is to evaluate how PPARγ agonist administration could reduce local and systemic inflammatory response after I/R injury during aortic supraceliac clamping in animal model. Methods Our model includes 16 rats divided as follows: 8 rats in the placebo control group (PlacG) were operated on without having been administered of any drugs during the preoperative period, whereas the 8 rats in the pioglitazone group (PioG) were pretreated with pioglitazone. Renal and visceral ischemias were induced in the rats by supraceliac aortic clamping. Rats were sacrificed after surgery, and then, we collected blood samples to measure serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and one of the kidneys and a segment of the liver to perform histological analysis. Results Considering both cytokines in the PioG, there has been a negative trend in serum concentrations, whereas in the PlacG, we observed an increasing trend. The high standard deviation observed in our study is mainly due to the small population of the cohort. Histologic examination of the kidney showed more severe damage in the placebo group as compared to the PioG with more evident differences in tubular and tubulointerstitial scores. Conclusions Our observations show that administering pioglitazone can partially reduce secondary inflammatory response in the ischemic insult especially in endothelial and perivascular tissues.

SummaryWe aimed at challenging the prognostic accuracies of myeloperoxidase (MPO) and antibodies anti-apolipoprotein A-1 (anti-apoA-1 IgG), alone or in combination, for major adverse cardiovascular events (MACE) prediction, one year after carotid endarterectomy (CEA). In this prospective single centre study, 178 patients undergoing elective CEA were included. Serum anti-apoA-1 IgG and MPO were assessed by enzyme-linked immunosorbent assay prior to the surgery. Post-hoc determination of the MPO cut-off was performed by receiver operating characteristics (ROC) analyses. MACE was defined by the occurrence of fatal or non-fatal acute coronary syndromes or stroke during one year follow-up. Prognostic accuracy of anti-apoA-1 IgG was assessed by ROC curve analyses, survival analyses and reclassification statistics. During follow-up, 5% (9/178) of patients presented a MACE, and 29% (52/178) were positive for anti-apoA-1 IgG. Patients with MACE had higher median MPO and anti-apoA-1 IgG levels at admission (p=0.01), but no difference for the 10-year global Framingham risk score (FRS) was observed (p=0.22). ROC analyses indicated that both MPO and anti-apoA-1 IgG were significant predictors of subsequent MACE (area under the curve [AUC]: 0.75, 95% confidence interval [95%CI]: 0.61–0.89, p=0.01; and 0.74, 95%CI: 0.59–90; p=0.01), but combining anti-apoA-1 IgG positivity and MPO>857 ng/ml displayed the best predictive accuracy (AUC: 0.78, 95%CI: 0.65–0.91; p=0.007). It was associated with a poorer MACE-free survival (98.2% vs. 57.1%; p

Background The aim of our study was to assess, by means of an experimental model, whether different geometries in retrograde bypass and stent-graft deployment may affect upstream and downstream blood pressure in hybrid treatment. Methods An in vitro model of the arterial circulation has been prepared, which consists of a peristaltic pump, silicon tubes with geometrical and mechanical properties close to realistic arteries, a terminal reservoir kept at constant pressure, and a sequence of pressure transducers. The system allows us to study the pressure wave propagation in physiological conditions and simulate the patient’s conditions as a result of debranching in 2 different configurations. Results In configuration 1, the mean pressure value (Kpa) was 4.72 in silicone tube before stent graft and debranching, 4.59 in visceral and renal bypass, and 4.38 in silicone tube after stent graft and debranching. In configuration 2, the mean pressure value (Kpa) was 5.22 in silicone tube before stent graft and debranching, 4.48 in visceral and renal bypass, and 4.99 in silicone tube after stent graft and debranching. Conclusion The experimental data suggest that the debranching geometry and the material of the grafts and stent grafts change significantly the physiological arterial pressure possibly leading to an augmented pressure upstream of the stent grafts, owing to retrograde pressure waves toward the heart, and a decreased pressure downstream visceral and renal arteries.

Conflicting results have been reported about the clinical value of fluorodeoxyglucose (FDG) imaging in predicting the risk of rupture of abdominal aortic aneurysm (AAA). The present study tests the hypothesis that FDG uptake is low in asymptomatic noninflammatory AAA due to the low cell density in aneurysmal walls.Positron emission tomography (PET)/CT imaging was performed in 12 consecutive candidates for AAA surgical repair and in 12 age- and sex-matched controls. At intervention, aneurysmal walls were cut into three sequential blocks. Block A was frozen to cut three 5-μm slices for incubation with 2-3 MBq of FDG for 5 min. Block C was first incubated with the same tracer solution for the same time and subsequently frozen to cut three 5-μm slices. Autoradiographic images were coregistered with immunohistochemical pictures of cell density, type and DNA synthesis as assessed on block B.No visible uptake in abdominal aorta occurred in any patient or control subject. Immunohistochemistry documented a severe loss of wall structure, with low numbers of cells. Tracer retention directly correlated with overall cell density and with prevalence of cells synthesizing DNA. The metabolic nature of FDG uptake was confirmed by the selective effect of preliminary freezing that decreased tracer content by 90% in regions with high cell density and only by 34% in cold acellular areas.The loss of tissue structure and the marked decrease in cell density account for the low prevalence of positive findings at FDG PET imaging, at least in asymptomatic patients bearing AAAs whose diameter is close to surgical indication.

Objectives Abdominal aortic aneurysm (AAA) is defined as a localized dilatation of an aortic vessel. Though predominantly asymptomatic, it is a chronic degenerative condition associated with life-threatening risk of rupture. The early diagnosis of AAA, ie, before it ruptures, is therefore important; a simple, effective diagnostic method is ultrasound examination. To assess the benefit of screening in Italy, we developed a cost-effective Markov model comparing screening vs nonscreening scenarios. Methods A 13-health-states Markov model was developed to compare two cohorts of 65- to 75-year-old men: the first group undergoing screening for AAA by means of ultrasound (US), the second following the current practice of incidental detection. The following health states were distinguished: no AAA, unknown small AAA (3-3.9 cm), followed-up small AAA (1 year), unknown medium-sized AAA (4-4.9 cm), followed-up medium-sized AAA (6 months), unknown large AAA (>5 cm), elective repair, emergency repair, postelective-repair AAA, postemergency-repair AAA, rejected large AAA, and death. Transitions between health states were simulated by using 6-month cycles. Transition probabilities were derived from a literature review of relevant randomized controlled trial and from a screening program that is currently ongoing at San Martino Hospital in Genoa, Italy. The Italian National Health Service (NHS) perspective was adopted and incremental cost per life-year saved was calculated with a lifetime horizon; costs and health benefits were discounted at an annual rate of 3% from year 2 onward. Uncertainty surrounding the model inputs was tested by means of univariate, multivariate, and probabilistic sensitivity analyses. Results Considering an attendance rate of 62%, the individual cost per invited subject was €60 (US $83.2); 0.011 additional quality adjusted life years (QALY) were gained per patient in the screened cohort, corresponding to an incremental cost-effectiveness ratio (ICER) of €5673/QALY (US $7870/QALY). The results were sensitive to some parameter variations but consistent with the base case scenario. They suggest that on the basis of a willingness-to-pay threshold of €50,000/QALY, screening for AAA is cost-effective, with a probability approaching 100%. Conclusions As in economic evaluations developed in other countries, such as the UK, Canada, and The Netherlands, setting up a screening program for AAA can be considered cost-effective from the Italian NHS perspective.

Aims Anti-Apolipoprotein A-1 auto-antibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high cardiovascular risk. The potential relationship between anti-ApoA-1 IgG and plaque vulnerability remains elusive. Thus, we aimed to investigate the role of anti-ApoA-1 IgG in plaque vulnerability. Methods and results Potential relationship between anti-ApoA-1 IgG and features of cardiovascular vulnerability was explored both in vivo and in vitro. In vivo , we investigated anti-ApoA-1 IgG in patients with severe carotid stenosis ( n = 102) and in ApoE−/− mice infused with polyclonal anti-ApoA-1 IgG. In vitro , anti-ApoA-1 IgG effects were assessed on human primary macrophages, monocytes, and neutrophils. Intraplaque collagen was decreased, while neutrophil and matrix metalloprotease (MMP)-9 content were increased in anti-ApoA-1 IgG-positive patients and anti-ApoA-1 IgG-treated mice when compared with corresponding controls. In mouse aortic roots (but not in abdominal aortas), treatment with anti-ApoA-1 IgG was associated with increased lesion size when compared with controls. In humans, serum anti-ApoA-1 IgG levels positively correlated with intraplaque macrophage, neutrophil, and MMP-9 content, and inversely with collagen. In vitro , anti-ApoA-1 IgG increased macrophage release of CCL2, CXCL8, and MMP-9, as well as neutrophil migration towards TNF-α or CXCL8. Conclusion These results suggest that anti-ApoA-1 IgG might be associated with increased atherosclerotic plaque vulnerability in humans and mice.

Aims The activation of cannabinoid receptor type 2 (CB2)-mediated pathways might represent a promising anti-atherosclerotic treatment. Here, we investigated the expression of the endocannabinoid system in human carotid plaques and the impact of CB2 pharmacological activation on markers of plaque vulnerability in vivo and in vitro . Methods and results The study was conducted using all available residual human carotid tissues (upstream and downstream the blood flow) from our cohort of patients symptomatic ( n = 13) or asymptomatic ( n = 27) for ischaemic stroke. Intraplaque levels of 2-arachidonoylglycerol, anandamide N -arachidonoylethanolamine, N -palmitoylethanolamine, N -oleoylethanolamine, and their degrading enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) were not different in human plaque portions. In the majority of human samples, CB1 (both mRNA and protein levels) was undetectable. In downstream symptomatic plaques, CB2 protein expression was reduced when compared with asymptomatic patients. In these portions, CB2 levels were inversely correlated ( r = −0.4008, P = 0.0170) with matrix metalloprotease (MMP)-9 content and positively ( r = 0.3997, P = 0.0174) with collagen. In mouse plaques, CB2 co-localized with neutrophils and MMP-9. Treatment with the selective CB2 agonist JWH-133 was associated with the reduction in MMP-9 content in aortic root and carotid plaques. In vitro , pre-incubation with JWH-133 reduced tumour necrosis factor (TNF)-α-mediated release of MMP-9. This effect was associated with the reduction in TNF-α-induced ERK1/2 phosphorylation in human neutrophils. Conclusion Cannabinoid receptor type 2 receptor is down-regulated in unstable human carotid plaques. Since CB2 activation prevents neutrophil release of MMP-9 in vivo and in vitro , this treatment strategy might selectively reduce carotid vulnerability in humans.

(2011). Screening for Abdominal Aortic Aneurysm. Questions and Results. Acta Chirurgica Belgica: Vol. 111, No. 1, pp. 7-10.

Background and Purpose— The concept of “vulnerable plaque” has been extended to the more recent definition of the “cardiovascular vulnerable patient,” in which “intraplaque” and “systemic” factors contribute to the cumulative risk of acute cardiovascular events. Thus, we investigated the possible role of systemic and intraplaque inflammation in patients asymptomatic versus symptomatic for ischemic stroke. Methods— Regions upstream and downstream the blood flow were isolated from internal carotid plaques of patients asymptomatic (n=63) or symptomatic (n=18) for ischemic stroke. Specimens were analyzed for lipid, collagen, macrophage, lymphocyte, neutrophil, mast cell and smooth muscle cell content, and chemokine and cytokine mRNA expression. Chemokine receptors and adhesion molecules were assessed on circulating leukocytes by flow cytometry. Systemic inflammatory markers and biochemical parameters were measured on total blood, plasma, and serum. Results— Tumor necrosis factor-α and CCL5 serum levels as well as intercellular adhesion molecule-1 expression on circulating neutrophils were increased in symptomatic as compared with asymptomatic patients. Collagen content and smooth muscle cell infiltration were decreased in symptomatic plaques. In upstream regions of symptomatic plaques, lipid content and lymphocyte infiltration were increased. In downstream regions of symptomatic plaques, macrophage, neutrophil, and mast cell infiltration were increased. Intraplaque collagen content was positively correlated with smooth muscle cell infiltration and inversely correlated with macrophages, neutrophils, or serum tumor necrosis factor-α. Collagen reduction in downstream regions and serum tumor necrosis factor-α were independently associated with the likelihood of being symptomatic. Conclusions— Inflammatory mediators are increased in ischemic stroke. Despite statistically significant, the correlation between tumor necrosis factor-α serum level and intraplaque vulnerability was weak and probably of limited biological importance.

A 56-year-old man presented with abdominal pain in the left lower quadrant. Computed tomography angiography showed the presence of an iliac axis dissection. Two Viabahn (W. L. Gore & Associates, Flagstaff, Ariz) covered stents were placed, starting from the beginning of the left common iliac artery to the iliac bifurcation, closing the proximal dissection tear in the left common iliac artery. A self-expandable EverFlex stent (EV3-Covidien, Plymouth, Minn) was then placed, bridging the covered stent and the left external iliac artery, covering the re-entry tear. There were no postoperative complications. During follow-up, we observed a progressive and complete thrombosis of the false lumen in 12 months.

SummaryHumoral autoimmune-mediated inflammation plays a role in atherogenesis, and potentially in arterial thrombosis. Anti-apolipoprotein A-1 (apoA-1) IgG have been reported to represent emergent mediators of atherogenesis through Toll-like receptors (TLR) 2, 4 and CD14 signalling. We investigated the role of anti-apoA-1 IgG on tissue factor (TF) expression and activation, a key coagulation regulator underlying atherothrombosis. Atherothrombosis features were determined by immunohistochemical TF staining of human carotid biopsies derived from patients with severe carotid stenosis undergoing elective surgery (n=176), and on aortic roots of different genetic backgrounds mice (ApoE-/-; TLR2-/-ApoE-/- and TLR4-/-ApoE-/-) exposed to passive immunisation with anti-apoA-1 IgG. Human serum levels of anti-apoA-1 IgG were measured by ELISA. In vitro, on human-monocyte-derived-macrophages (HMDM) the anti-apoA-1 IgG increased TF expression and activity were analysed by FACS and chromogenic assays in presence of different pharmacological inhibitors. Human serum anti-apoA-1 IgG levels significantly correlated to intraplaque TF expression in carotid biopsies (r=0.31, p

Background Different cut-off values of serum lipoprotein (a) [Lp (a)] were recently identified to better stratify cardiovascular risk categories. Both pathophysiological and prognostic values of Lp (a) remain unclear. Materials and methods Here, the prognostic value of Lp (a) and its correlation with intraplaque features were assessed in patients with severe carotid artery stenosis undergoing endarterectomy (n = 180). The cut-off value of 10 mg/dL for serum Lp (a) was selected to predict 24-month follow-up acute coronary syndrome (ACS). In addition, the association between serum Lp (a) and intraplaque lipids, collagen, inflammatory and vascular cells was assessed. Serum Lp (a) levels were measured by nephelometric assay. Results Patients with high Lp (a) had similar comorbidities, medications and laboratory parameters as compared to low Lp (a) levels. At 24-month follow-up, patients with high Lp (a) had more ACS as compared to low levels. Histological parameters within plaques were comparable in the study groups. No significant correlation between Lp (a) serum levels and intraplaque parameters was found, except for a weak positive association with smooth muscle cells in upstream plaque portions. When adjusted for gender, the presence of dyslipidaemia and chronic coronary artery disease, Lp (a) ≥10 mg/dL remained predictive for ACS. Conclusions Lp (a) determination could be a useful tool to predict ACS in patients with severe carotid stenosis.

Aneurysms of the anterior tibial artery are rare. We will describe a case of a woman with an asymptomatic true aneurysm of the anterior tibial artery. The patient presented with a pulsatile mass in the lateral face of the distal portion of the left leg, and both ultrasound examination and computed tomography angiography scan showed a giant aneurysm of the anterior tibial artery. We chose open treatment.

Open thoracoadbominal aortic aneurysm (TAAA) treatment presents a high complication rate such as spinal cord ischemia. Surgical technique includes the temporary occlusion of intercostal arteries with a balloon. In rare cases, the arterial injury can lead to development of an intercostal artery aneurysms (ICAA), probably because of a thin artery wall and a too high insufflation pressure. The aim of this study was to report the case of a 78-year-old woman, who underwent an open type-II TAAA repair and developed an asymptomatic 11-mm ICAA. According to the diameter, we successfully treated the patient with platinum coils, obtaining the complete aneurysm exclusion and an uneventful recovery.

BACKGROUND The aim of this paper was to compare in a retrospective study the outcome of aortoaortic graft (straight graft) versus aortoiliac graft (bifurcated graft) with regards to periprocedural and 30-day after surgery complications. METHODS From January 2004 to December 2009 377 patients underwent elective open surgery for infrarenal abdominal aortic aneurysm. Data were collected in a dedicated database. Group A includes patients treated with straight graft (N.=186) whereas group B, patients treated with bifurcated graft (N.=191). Outcome data include duration of surgical procedure, blood loss, peri- and postprocedural complications, hospital stay, 30-day mortality and complications. Following some authors, we set our cut-off for choosing a bifurcated graft when one or both Iliac Arteries were wider than 18 mm in diameter and the patient had a reasonable life expectancy. RESULTS Duration of surgical procedure was 183 minutes in the group A vs. 216 minutes in the group B (P

BACKGROUND: To assess the prevalence of increased (18)F-fluorodeoxyglucose (FDG) uptake in aneurysmal walls, adopting a case-control approach in a population of asymptomatic patients with abdominal aortic aneurysm (AAA). METHODS: This study included 40 males (mean age: 74 years, range: 59-93 years), consecutive, white Caucasian patients, with asymptomatic infrarenal AAA. The mean diameter of AAA was 4.9 cm (range: 4.8-5.4 cm), detected by computed tomography (CT) scan. Control Subjects: 44 age-matched controls subjects (mean age: 71 years, range: 59-85 years, 24 males, 20 females) who were selected according to a case-control criterion among a population of patients without any clinical evidence of atherosclerotic disease. Patients and controls underwent simultaneous FDG-positron emission tomography (PET) and CT imaging from the skull base to the femoral neck by using an integrated PET/CT scanner. PET/CT studies were analysed both visually and quantitatively. For quantitative analysis, circular CT-based regions of interest (ROIs) were drawn on the AAA, on all the aortic segments, and on the large vessel included in the study (carotid, subclavian, and iliac arteries). FDG uptake was quantified by calculating the mean and maximum standardized uptake values (SUVs) within each ROI and normalizing for the blood-pool SUV to obtain the final target-to-background ratio. Arterial calcium load was graded according to a semiquantitative five-point scale based on calcification of the arterial ring. RESULTS: Metabolic activity in the aneurysmal aortic segment was even lower with respect to both the adjacent--nonaneurysmal--samples of patient group and the corresponding arterial segments of control subjects (P < 0.001 and P < 0.01, respectively). In visual analysis, no patients showed an increased focal uptake of degree adequate to identify the aneurysmal arterial wall. AAA patients showed significantly higher values of total calcium load (ACL) than controls in ascending aorta and subclavian and iliac arteries (P < 0.01), and only in AAA patient group, a significant correlation was present between values of ACL in both iliac arteries and abdominal aorta on one side and wall metabolic activity in the same arteries on the other (P < 0.05). CONCLUSIONS: In conclusion, our results suggest that FDG hot spot, as well an increased diffuse uptake of FDG, in PET/CT studies is an extremely rare finding in patients with AAA of diameter close to surgical indications.

Background Monocyte activation, macrophage infiltration, vascular oxidative stress and matrix proteolysis are inflammatory key steps contributing to abdominal aortic aneurysm (AAA) development. A phenotypical and functional heterogeneity is recognizable in monocytes by the differential expression of surface molecules: CD62L− subset corresponds to activated monocytes, while CD143/ACE surface expression increases during their differentiation into macrophages. In this work, Resveratrol, which is an antioxidant polyphenol with vasoprotective properties, has been evaluated for its potential to limit aneurysm development and monocyte-dependent inflammatory response in a model of elastase-induced AAA. Methods Male Sprague-Dawley rats received Resveratrol (10 mg/kg/die) (Rsv group, n = 15) or vehicle (ethanol) alone (Et-OH group, n = 15) continuously from 7 d before until 14 d after the AAA induction with elastase; five littermates were used as untreated control group (Ctr group, n = 5). At the end of treatment, CD143 and CD62L monocyte expression was analyzed by flow cytometry, serum antioxidant capacity was evaluated using the TRAP method and circulating TNFα, and MMP-9 were measured with ELISA and gel zymography, respectively. Aortas were subjected to histology and immunohistochemistry for morphological analysis, macrophage infiltration, and MMP-9, TNFα, and VEGF expression. Results Resveratrol counteracted the CD62L-monocyte subset expansion, CD143 monocyte expression, and circulating levels of MMP-9 activity and TNFα associated to AAA induction. Similarly, treatment with Resveratrol significantly attenuated AAA expansion, vessel wall macrophage infiltration and MMP-9, VEGF, and TNFα expression, compared with AAA from Et-OH group. Conclusions Resveratrol limited the monocyte-dependent inflammatory response, macrophage differentiation and aortic lumen enlargement in elastase-induced AAA. These data suggest that Resveratrol might be tested in selected patients with small AAA to modulate the early systemic and local inflammatory response associated to AAA progression.

The incidence of Abdominal Aortic Aneurysms (AAA) varies between 3% and 6% of the elder population, especially men over sixty years of age. Moreover, familiarity, smoking and peripherical atherosclerosis are known to be important risk factors. In the United States AAA ruptures cause about 9000 deaths every year. About 33000 elective surgical treatments per year are performer with a mortality of 1400–2800 patients. The percentage of success of surgical treatment remains strictly related to the diagnosis of the stage of the AAA. Mortality rate for elective surgical intervention (asymptomatic aneurysms) is 5%. On the contrary mortality rate for emergency surgical intervention is about 70% [1]. Selection of candidates to surgery is still based on measurement of aortic diameter, with a threshold size of 55 mm. The rate of AAA rupture increases from 21% to 46% for diameters between 50 and 70 mm. The main diagnostic tool currently adopted is the CT that allows for obtaining precise information regarding the dimensions and the morphology of the aneurysm and possible proximal extension (juxarenal, infrarenal, thorac-abdominal) and distal (iliac and hypogastric) of the aneurysm, intramural thrombus. Since rupture occurs when the aneurysm wall fails to withstand the forces acting on it, in vivo data on AAA wall pathology could identify patients at risk of rupture. End-stage aneurysm disease and especially aneurysm rupture are characterized by extensive inflammation of the arterial wall. Although the stimulus for this enhanced infiltration is not known, recent insights into the pathophysiology of aneurysm formation, growth, and rupture indicate a close relationship between increased mechanical stress and the activation of infiltrated lymphocytes and macrophages [2]. This increased inflammatory activity results in the progressive breakdown of the aortic wall, aneurysm dilatation and, ultimately, rupture. A further complication is represented by the mechanical actions exerted on the arterial wall by the internal blood flow. The blood flow is strongly influenced by the presence of an AAA, which modifies significantly the geometry of the aorta. Shear stresses and pressure are important factors to understand the formation and evolution of an AAA. Another important aspect is related to the formation of the thrombus that is thought to be relevant for the wall degeneration, see [3] for a comprehensive review of these topics.Copyright © 2010 by ASME

Over a three-year period we performed 630 carotid endarterectomy procedures in 588 patients. From these we selected 90 patients (group A) who fulfilled the criteria for discharge one day after surgery. These patients were given an electronic blood pressure meter, a videophone for use at home and an antihypertensive drug (amlodipine). Using web-based videoconferencing, we monitored the patients every 4 hours for the first two days. The other 498 patients (group B) were discharged on the second postoperative day. There were no significant differences between the groups in demographic characteristics, risk factors, carotid lesions, operative time, postoperative complications or blood loss. No cervical hematomas developed in group A. No patients needed to be readmitted because of major complications relating to the carotid endarterectomy. During the video-communication, 28 patients (31%) with a hypertensive crisis were treated by administration of amlodipine. At discharge, a questionnaire showed that there was a feeling of insecurity in both groups: 87% in group A vs. 79% in group B ( P > 0.05). In group A, insecurity decreased after the first video connection and disappeared after the 8th day postoperatively. Telemedicine appears feasible and useful in carotid endarterectomy and may have other applications in vascular surgery care.

Objectives: to investigate the utility of assessing Health-Related Quality of Life (HRQoL) in a large group of subjects participating in a screening program for aneurysm and the relationship between HRQoL, diagnosis of aneurysm and related risk factors. Methods: subjects involved in this screening program were submitted the EQ-5D questionnaire to report their own HRQoL. HRQoL was reported also a second time by the subjects who were diagnosed with aneurysm during screening and who returned for a monitoring follow up visit a few months later. We evaluated compliance with HRQoL data collection and performed multiple regression analyses in order to investigate the possible relationship between demographic and clinical data with HRQoL. Results: 1,633 subjects screened (6.1% diagnosed with aneurysm) and 125 subjects diagnosed with aneurysm and attending a follow-up visit reported their HRQoL. Completion of the EQ-5D questionnaire was well accepted by both physicians-and-subjects-undergoing-screening.-HRQoL- was-not-significantly-different-between-the-screening-and-followup visits, on adjusting for age and sex. At the screening visit, HRQoL was associated with ASA class, heart condition, BMI-and-respiratory-diseases.-No-associations-were- found-at-the-follow-up-visit. Conclusion: Assessing HRQoL in screening programs is feasible and well accepted and add useful information on health of large numbers of subjects from general population. This could be considered as a routine approach to optimizing the informative role of screening programs in guiding other investigations or interventions.

SummaryAngiotensin (Ang)-(1–7), acting through the receptor Mas, has atheroprotective effects; however, its role on plaque vulnerability has been poorly studied. Here, we investigated the expression of the renin-angiotensin system (RAS) components in stable and unstable human carotid plaques. In addition, we evaluated the effects of the chronic treatment with an oral formulation of Ang-(1–7) in a mouse model of shear stress-determined carotid atherosclerotic plaque. Upstream and downstream regions of internal carotid plaques were obtained from a recently published cohort of patients asymptomatic or symptomatic for ischaemic stroke. Angiotensinogen and renin genes were strongly expressed in the entire cohort, indicating an intense intraplaque modulation of the RAS. Intraplaque expression of the Mas receptor mRNA was increased in the downstream portion of asymptomatic patients as compared to corresponding region in symptomatic patients. Conversely, AT1 receptor gene expression was not modified between asymptomatic and symptomatic patients. Treatment with Ang-(1–7) in ApoE-/- mice was associated with increased intraplaque collagen content in the aortic root and low shear stress-induced carotid plaques, and a decreased MMP-9 content and neutrophil and macrophage infiltration. These beneficial effects were not observed in the oscillatory shear stress-induced plaque. In vitro incubation with Ang-(1–7) did not affect ICAM-1 expression and apoptosis on cultured endothelial cells. In conclusion, Mas receptor is up regulated in the downstream portions of human stable carotid plaques as compared to unstable lesions. Treatment with the oral formulation of Ang-(1–7) enhances a more stable phenotype in atherosclerotic plaques, depending on the local pattern of shear stress forces.