J.S. Lindholt

FAILURE TO DEMONSTRATE CHLAMYDIA PNEUMONIAE IN SYMPTOMATIC ABDOMINAL AORTIC ANEURYSMS BY A NESTED POLYMERASE CHAIN REACTION (PCR)

OBJECTIVE To investigate whether Chlamydia pneumoniae is present in symptomatic abdominal aortic aneurysms (AAA). METHOD AND MATERIALS After optimisation of DNA extraction procedures an inhibitor-controlled nested polymerase chain reaction (PCR) amplifying fragments of the gene encoding the C. pneumoniae specific major outer membrane protein was performed on 124 wall-specimens from 20 patients with symptomatic AAA. RESULTS None of the specimens contained C. pneumoniae-specific DNA. Minor inhibition of the PCR was noticed especially in media specimens. CONCLUSION Using a sensitive and specific nested PCR, we were not able to detect C. pneumoniae in symptomatic AAA. The failure to detect C. pneumoniae in symptomatic AAA, combined with previously reported positive findings in atherosclerotic lesions, supports the hypothesis that AAA and atherosclerosis might be two different disease entities.

Mast Cell Tryptase Deficiency Attenuates Mouse Abdominal Aortic Aneurysm Formation

Rationale: Mast cells (MCs) contribute to the formation of abdominal aortic aneurysms (AAAs) by producing biologically active mediators. Tryptase is the most abundant MC granule protein and participates in MC activation, protease maturation, leukocyte recruitment, and angiogenesis—all processes critical to AAA pathogenesis. Objective: To test the hypothesis that tryptase participates directly in AAA formation. Methods and Results: Immunohistochemistry demonstrated enhanced tryptase staining in media and adventitia of human and mouse AAA lesions. Serum tryptase levels correlated significantly with the annual expansion rate of AAA before (r=0.30, P=0.003) and after (r=0.29, P=0.005) adjustment for common AAA risk factors in a patient follow-up study, and associated with risks for later surgical repair or overall mortality before (P=0.009, P=0.065) and after (P=0.004, P=0.001) the adjustment. Using MC protease-6–deficient mice (Mcpt6−/−) and aortic elastase perfusion-induced experimental AAAs, we proved a direct role of this tryptase in AAA pathogenesis. Whereas all wild-type (WT) mice developed AAA at 14 or 56 days postperfusion, Mcpt6−/− mice were fully protected. AAA lesions from Mcpt6−/− mice had fewer inflammatory and apoptotic cells, and lower chemokine levels, than did those from WT mice. MC from WT mice restored reduced AAA lesions and lesion inflammatory cell content in MC–deficient KitW-sh/W-sh mice, but those prepared from Mcpt6−/− mice did not. Mechanistic studies demonstrated that tryptase deficiency affected endothelial cell (EC) chemokine and cytokine expression, monocyte transmigration, smooth-muscle cell apoptosis, and MC and AAA lesion cysteinyl cathepsin expression and activities. Conclusions: This study establishes the direct participation of MC tryptase in the pathogenesis of experimental AAAs, and suggests that levels of this protease can serve as a novel biomarker for abdominal aortic expansion.

Serum-elastin-peptides as a predictor of expansion of small abdominal aortic aneurysms.

OBJECTIVE To optimise the indication and time for operation for abdominal aortic aneurysm (AAA), we analysed whether or not serum-elastin-peptides (SEP) could be a potential predictor for expansion. MATERIALS AND METHODS Four thousand, four hundred and four 65-73-year-old males were invited for screening to detect an AAA. Three thousand, three hundred and thirty-four attended (76%). One hundred and forty-one had AAA, and 19 > 5 cm in diameter were referred for immediate operation. The remaining 122 AAA were offered an annual follow-up. Ninety-nine were later asked for a blood-sample, 83 attended. SEP was determined using an ELISA-technique. The observer was blinded to the SEP result. RESULTS The average expansion was 2.6 mm/year, and 10 (8.1) were referred for operation because of a diameter of > 5 cm. SEP were positively correlated to expansion (R = 0.4, F = 14.65). In multiple regression analyses, AAA size, SEP, beta-agonist-treatment, and FEV1, but not beta-blockers, were predictors of expansion. SEP remained a relatively strong predictor (F = 13.13). CONCLUSIONS Serum-elastin-peptides seem to predict expansion, but a larger, longer study is needed to establish clinical recommendations.

High Proportions of Coexisting Aortic Dilations Call for Total Aortic Scan

An aortic dilation is a potentially lethal condition because it may lead to rupture or dissection [(1)][1]. Dilations on the ascending aorta (AsAo) develop secondary to cystic medial necrosis, whereas dilations on the descending aorta (DeAo) and abdominal aorta (AbAo) are often associated with

Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior.

Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 × 10−8), including previously identified SNPs at 15q25 represented by rs1051730[A] (effect size = 0.80 CPD, P = 2.4 × 10−69), and SNPs at 19q13 and 8p11, represented by rs4105144[C] (effect size = 0.39 CPD, P = 2.2 × 10−12) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 × 10−8), respectively. Among the genes at the two newly associated loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), all of which have been highlighted in previous studies of smoking and nicotine dependence. Nominal associations with lung cancer were observed at both 8p11 (rs6474412[T], odds ratio (OR) = 1.09, P = 0.04) and 19q13 (rs4105144[C], OR = 1.12, P = 0.0006).