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.

Utilización de stents direccionadores de flujo en aneurismas viscerales / Use of flow-diverting stents in visceral aneurysms

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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.

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.

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.

Seguimiento a cinco años de los pacientes ASA IV intervenidos de aneurisma de aorta infrarrenal / Five years follow-up of patients ASA IV operated of infrarenal aortic aneurysm

Objetivos. Uno de los argumentos esgrimidos para justificar la utilización de endoprótesis en pacientes con aneurismas de aorta es que obtengan una clasificación ASA IV en la valoración preoperatoria de riesgo anestésico. Para rechazar o defender este criterio hemos realizado un estudio retrospectivo de este tipo de pacientes intervenidos en el período 1991-1995 con el fin de conocer, de esta forma, su evolución. Pacientes y métodos. Se consideraron ASA IV 36 pacientes de un total de 126 intervenidos entre 1991 y 1995 de aneurisma de aorta infrarrenal. Se excluyeron los pacientes intervenidos urgentemente y los casos de pinzamiento suprarrenal. La edad media fue de 69,6 y sólo uno era del sexo femenino. Los factores de riesgo predominante fueron el tabaquismo y la hipertensión. La enfermedad asociada más frecuente fue la cardiopatía, sobre todo la isquémica, y la limitación crónica al flujo aéreo. Resultados. La mortalidad hospitalaria fue del 2,7 por ciento, la mortalidad al año fue del 8,3 por ciento, a los tres años del 36 por ciento, y a los cinco años, del 55,5 por ciento. La causa más frecuente fue el cáncer, seguido del infarto de miocardio. Conclusiones. La mortalidad operatoria de los ASA IV en nuestra serie es baja, aceptable y similar a la mortalidad global de los aneurismas, entre ellos los ASA III. La clasificación ASA presenta un bajo valor predictivo en cuanto a la mortalidad quirúrgica. Ambas conclusiones se deben a la sobrevaloración del riesgo en alguno de nuestros pacientes y, por lo tanto, la clasificación ASA no es el método adecuado de guía para la inclusión de pacientes en el tratamiento con endoprótesis aórtica; ésta debe basarse en criterios anatómicos y siempre dentro de un estudio controlado. (AU)