Circulating CCL20 as a New Biomarker of Abdominal Aortic Aneurysm.

Autoimmunity appears to play a role in abdominal aortic aneurysm (AAA) pathology. Although the chemokine CCL20 has been involved in autoimmune diseases, its relationship with the pathogenesis of AAA is unclear. We investigated CCL20 expression in AAA and evaluated it as a potential biomarker for AAA. CCL20 was measured in plasma of AAA patients (n = 96), atherosclerotic disease (AD) patients (n = 28) and controls (n = 45). AAA presence was associated with higher plasma levels of CCL20 after adjustments for confounders in the linear regression analysis. Diagnostic performance of plasma CCL20 was assessed by ROC curve analysis, AUC 0.768 (CI:0.678-0.858; p<0.001). Classification and regression tree analysis classified patients into two CCL20 plasma level groups. The high-CCL20 group had a higher number of AAA than the low-CCL20 group (91% vs 54.3%, p< 0.001). mRNA of CCL20 and its receptor CCR6 were higher in AAA (n = 89) than in control aortas (n = 17, p<0.001). A positive correlation was found between both mRNA in controls (R = 0674; p = 0.003), but not in AAA. Immunohistochemistry showed that CCR6 and CCL20 colocalized in the media and endothelial cells. Infiltrating leukocytes immunostained for both proteins but only colocalized in some of them. Our data shows that CCL20 is increased in AAA and circulating CCL20 is a high sensitive biomarker of AAA.

Influence of cardiovascular risk factors on levels of matrix metalloproteinases 2 and 9 in human abdominal aortic aneurysms.

OBJECTIVE: To evaluate the influence of cardiovascular risk factors on levels of matrix metalloproteinases (MMP) 2 and 9 in human abdominal aortic aneurysms (AAA). METHODS: Aortic samples were collected from patients who underwent AAA repair (n = 89). Patients were stratified according to the maximum transverse aorta diameter: small diameter (<55 mm), moderate diameter (55-69.9 mm) and large diameter (≥70 mm). Aortic walls were studied using real-time PCR and immunohistochemistry. MMP-2, MMP-9, α-actin, CD45, and CD68 transcript levels were determined relative to ß-actin. Quantitative data were expressed as median (IQ-range). RESULTS: No differences were found in MMP-2 expression between the patient groups, which was mainly associated with vascular smooth muscle cells (VSMC); however, MMP-9 displayed the maximum level in the moderate-diameter group, associated with infiltrating macrophages. Current smoking (CS) and renal insufficiency (RI) significantly increased local levels of MMP-2 (CS 349.5 [219.5-414.1] vs. no-CS 184.4 [100.0-320.5]; p < .008; RI 286.8 [189.6-410.8] vs. no-RI 177.3 [99.3-326.9]; p = .047). Nevertheless, after stepwise linear regression analysis only CS remained as an independent variable predicting local levels of MMP-2 (p = .002). No risk factors influenced local levels of MMP-9. CONCLUSIONS: The results show that local levels of MMP-2, an important factor for AAA development, were increased in current smoking AAA patients. MMP-2 was mainly associated with VSMC. It is suggested that MMP-2 could contribute significantly to the increased AAA growth rate observed in current smoking patients. These findings support inclusion of smokers in screening for aneurysmal disease, and emphasize the need for more aggressive monitoring of aneurysmal disease outside the surgical range in patients who smoke at the time of diagnosis and in those who continue to smoke during follow-up.

A computational fluid dynamics study on hemodynamics for different locations of the distal anastomosis of a bypass nearby a collateral vessel in the femoropopliteal area.

Revascularization of the femoropopliteal sector is often performed by the placement of a bypass. In this paper, we have studied the effects of hemodynamics on patency of the bypass for different positions of the distal anastomosis close to a collateral artery. Computational fluid dynamics (CFD) are used for this study. The cardiac cycle-averaged wall shear stress (WSS) and oscillation index (OSI) have been analyzed. Low WSS and high OSI may increase the risk of intimal hyperplasia (IH), which may reduce bypass patency. From the CFD simulations, spots of low WSS and high OSI are found within and near the entrance of the collateral artery, near the suture line, at the floor, toe, and heel. We regarded flow ratios of 20:80 and of 35:65. It is found that for the high flow ratio anastomosis located proximal to the collateral artery is clearly more advantageous. However for the low flow ratio anastomosis located distal to the collateral artery seems to be slightly more advantageous, the results are less conclusive. One of the studied flow geometries has been validated by in vitro experiments using a time resolved particle image velocimetry technique. Velocity fields from these experiments are in good agreement with the CFD results.

Healthcare quality indicators of peripheral artery disease based on systematic reviews.

OBJECTIVES: Peripheral artery disease (PAD) is a major health problem whose clinical management includes multiple options regarding risk factor control, diagnosis, and medical and surgical treatment. The aim was to generate indicators based on systematic reviews to evaluate the quality of healthcare provided in PAD. METHODS: Electronic searches were run for systematic reviews in The Cochrane Library (Issue 6, 2011), MEDLINE, EMBASE, and other databases (up to June 2011). Conclusive systematic reviews of high methodological quality were selected to formulate clinical recommendations. Indicators were derived from clinical recommendations with moderate to very high strength of evidence as assessed by the GRADE system. RESULTS: From 1,804 reviews initially identified, 29 conclusive and high-quality systematic reviews were selected and nine clinical recommendations were formulated with a moderate to very high strength of recommendation. Six indicators were finally generated: four on pharmacological interventions, antiplatelet agents, naftidrofuryl, cilostazol, and statins; and two lifestyle interventions, exercise and tobacco cessation. No indicators were derived for diagnostic tests or surgical techniques. Most indicators targeted patients with intermittent claudication. CONCLUSIONS: These quality indicators will help clinicians to assess the appropriateness of healthcare provided in PAD. The development of evidence-based indicators in PAD is limited by the lack of methodological quality of the research in this disease, the inconclusiveness of the evidence on diagnostic and surgical techniques, and the dynamic nature of the vascular diseases field.

Métodos de estudio de las enfermedades complejas: aneurismas de la aorta abdominal / Methods for studying complex diseases: abdominal aortic aneurysm

Las enfermedades vasculares, particularmente el aneurisma de la aorta abdominal (AAA), tienen una base multifactorial compleja, donde múltiples interacciones entre factores genéticos y ambientales contribuyen al desarrollo de la enfermedad. Sin embargo, pese a los avances en la última década, nuestros conocimientos sobre la base genética de estas patologías son aún escasos. Este artículo presenta una revisión de los métodos para el estudio de las bases genéticas de las enfermedades vasculares focalizada en el AAA desde un enfoque de enfermedad compleja, y de índole multifactorial. La identificación y el análisis de los genes causantes de esta patología nos permitirán realizar una estratificación de los individuos con diferentes riesgos de desarrollar esta patología, mejorando las opciones preventivas y terapéuticas, lo que se traducirá en una mayor calidad de vida de las personas en riesgo(AU)

The aetiology of vascular diseases, such as abdominal aortic aneurysm (AAA), is complex and multi-factorial. The complexity derives from different genetic and environmental factors contributing to the development of these diseases. Despite the fact that a great effort has been made in the last decade to understand the genetic basis of these complex diseases there is still much to be learned. The present review deals with the methods that have been used to study the genetic bases of vascular diseases. In addition, we will focus on AAA as a complex multi-factorial disease. The identification of the genes involved in the pathophysiology of AAA will allow us to stratify individuals with different risks of developing disease, as well as improving preventive and therapeutic strategies. All of this will increase the quality of life of the persons who are in risk(AU)

Cambios en el perfil del paciente diabético hospitalizado en una sala de cirugía vascular y de los procedimientos quirúrgicos utilizados en 1985 y 2007 / Changes of the in-hospital diabetic patient profile in the employed in a vascular surgery department and surgical procedures between 1985 and 2007

Objetivos: 1. Conocer las características de los pacientes con piediabético hospitalizados en cirugía vascular durante los años 1985y 2007, los procedimientos quirúrgicos utilizados, la estancia mediay la mortalidad, y 2. Conocer el grado de control de la diabetes y losfactores de riesgo asociados en los mismos pacientes en 2007.Material y métodos: Se analizaron datos de la diabetes (tipo,tiempo de evolución, tratamiento y complicaciones), factores deriesgo, procedimientos quirúrgicos, estancia media y mortalidad enlos años 1985 y 2007. En 2007 se valoraron además: hemoglobinaglucosilada (HbA1c), perfil lipídico y presión arterial (PA). Resultados:Se evaluaron 162 pacientes (91 en 1985, 71 en 2007). Laprevalencia de complicaciones microangiopáticas, el número de fumadoresy los pacientes en tratamiento con insulina fueron superioresen 1985. La edad y prevalencia de hipertensión y dislipemiafueron mayores en 2007. La distribución por sexos y duración de ladiabetes fueron similares. En 1985 se practicaron más amputaciones,y en 2007 más cirugía conservadora, asociada o no a amputaciónmenor, y menos amputaciones, sobre todo mayores. En 2007no se practicaron simpatectomías lumbares, frecuentes en 1985. Lamortalidad y la estancia media fueron inferiores en 2007, pero sóloun 36% de pacientes tenía una HbA1c <7%, un 24% presentaba PAinferior al objetivo y un 29% cumplía objetivos lipídicos. Conclusiones:Los sujetos ingresados en 2007 presentan menos complicacionesde la diabetes que los de 1985 con el mismo tiempo deevolución. Ya no se realizan simpatectomías lumbares, se han reducidolas amputaciones, sobre todo mayores, y se realiza más cirugíarevascularizadora. En 2007 el grado de control de la diabetes, la PAy los lípidos es subóptimo(AU)

Objectives: To know: 1) The features of patients hospitalised fordiabetic foot in the department of vascular surgery, the years 1985and 2007, surgical procedures used, average stay and mortality.2) Metabolic control and associated cardiovascular risk factors of thesame patients in 2007. Material and methods: Data related todiabetes (type, time evolution, treatment, complications), other riskfactors, surgical procedures, average stay and mortality in the years1985 and 2007, were registered. In 2007 other parameters werealso registered: HbA1c, lipid profile and blood pressure. Results: Atotal of 162 diabetic patients were evaluated (91 in 1985 and 71 in2007). The prevalence of microangiopathic complications, currentsmokers and number of patients treated with insulin were higher in1985. Age, prevalence of hypertension and dyslipidemia were higherin 2007. Sex distribution and diabetes duration were similar. In1985 more amputations were carried out. In 2007 more conservativesurgery associated or not with minor amputation was executed,with less number of amputations (especially major). In 2007, lumbarsympathectomy was not performed, whereas it was frequent in1985. Mortality and average stay were reduced in 2007, but only 36% of subjects presented HbA1c <7%, only 24% presented bloodpressure below goals and only 29% had lipid profile below goals.Conclusions: Patients hospitalised in 1987 had more complicationsof diabetes than those hospitalised in 2007, with the sametime of evolution. Nowadays, lumbar sympathectomy has been abandoned,amputations have been reduced (especially major amputations)and more revascularization surgery is performed. In 2007,control of diabetes, lipids and blood pressure are suboptimal(AU)

Microsomal prostaglandin E synthase-1, which is not coupled to a particular cyclooxygenase isoenzyme, is essential for prostaglandin E(2) biosynthesis in vascular smooth muscle cells.

BACKGROUND: Prostaglandin (PG) E(2) induces expression of matrix metalloproteinases and angiogenic factors, thereby contributing to plaque instability. OBJECTIVE: To study the influence of cyclooxygenase (COX) and PGE synthase (PGES) isoenzyme expression on PGE(2) and PGI(2) biosynthesis in vascular smooth muscle cells (VSMC) in culture. METHODS: Cells were treated with human recombinant IL-1beta over different periods of time. Expression of PGI synthase, and COX and PGES isoenzymes was determined by real-time reverse transcriptase polymerase chain reaction and immunoblotting. Biosynthesis of prostanoids from exogenous or endogenous substrate was analyzed by high-performance liquid chromatography or enzyme-immunoassay after incubation of cells with labeled arachidonic acid or thrombin, respectively. RESULTS: Cytosolic PGES and microsomal PGES (mPGES) -1 and -2 were expressed in VSMC. PGES activity was mainly linked to mPGES-1. IL-1beta induced COX-2 and mPGES-1 with a different time course. VSMC ability to synthesize PGE(2) and PGI(2) fitted mPGES-1 and COX-2 expression, respectively. The ability of VSMC to produce PGI(2) was downregulated by mPGES-1 expression and was restored when mPGES-1 expression was silenced. Results from COX-1 and COX-2 silencing and selective inhibition showed that both COX-1 and COX-2 were involved in the biosynthesis of PGE(2) and their relative contribution depended on the time of incubation with IL-1beta. CONCLUSIONS: mPGES-1 is the main PGES responsible for PGE(2) biosynthesis by VSMC and its induction downregulates VSMC ability to produce PGI(2.) These results support the concept that under inflammatory conditions VSMC could significantly contribute to plaque instability and that mPGES-1 may be a target for therapeutic intervention in patients with cardiovascular risk.

Human vascular smooth muscle cells but not endothelial cells express prostaglandin E synthase.

In a previous work, we postulated that endothelial cells possess only the following 2 enzymes involved in prostanoid synthesis: cyclooxygenase and prostacyclin synthase. The present work focused on investigating the expression of prostaglandin (PG) E synthase (PGES) in vascular cells. After incubation of vascular smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) with [(14)C]arachidonic acid, the profile of prostanoid synthesis was assessed by HPLC. Untransformed PGH(2) released by the cells was evaluated as the difference in the formation of PGF(2alpha) in the incubations performed in the presence and in the absence of SnCl(2). Resting SMCs and SMCs stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha formed PGE(2) and PGI(2) (evaluated as 6-oxo-PGF(1alpha)), and in the presence of SnCl(2) only a small amount of PGE(2) was deviated toward PGF(2alpha). In contrast, resting and stimulated HUVECs produced PGI(2), PGE(2), PGF(2alpha), and PGD(2), and SnCl(2) completely diverted PGE(2) and PGD(2) toward PGF(2alpha). Reverse transcriptase-polymerase chain reaction analysis shows that mRNA encoding for PGES was not present in HUVECs and in endothelial cells from saphenous vein. Nevertheless, PGES was expressed in SMCs and induced by IL-1beta and TNF-alpha, and by PMA and LPS, although to a lesser extent. Whereas SMC stimulation led to an increase in the synthesis of PGE(2) and PGI(2) but not of untransformed PGH(2), stimulation of endothelial cells resulted in an enhanced release of the vasoconstricting prostanoid PGH(2).

[Aortobifemoral prostheses with "0" porosity. Results after 2 years' experience]. / Prótesis aortobifemorales porosidad "O". Resultados tras dos años de experiencia.

During the last years diverse types of Dacron prosthesis without porosity (because to be impregnated by different materials) have appeared. In the presented study, outcomes from three different types of prosthesis (differentiated by the impregnated material) were evaluated and a comparison with classical prosthesis was made.

[Effect of peripheral parenteral nutrition on the immediate postoperative period in surgery of the aortic sector]. / Efecto de la nutrición parenteral periférica en el postoperatorio inmediato de la cirugía del sector aórtico.

There is not an extensive literature about nutritional value in Vascular Surgery. In this study, efficacy and cost/benefit relation in the application of Peripheric Parenteral Nutrition (PPN) in postoperative of aortic surgery, are investigated through two randomized groups, in patients with aortoiliac obstructive arteriopathy and who needed an aortobifemoral bypass.