Rationale Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). Methods and Results Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

Use of EndoAnchors to treat existing and acute type Ia endoleaks and endograft migration was successful in most cases. Prophylactic use of EndoAnchors in patients with hostile aortic neck anatomy appears promising, but definitive conclusions must await longer term follow-up data.

Background and Purpose-We studied matrix metalloproteinases (MMP) 2, 8, and 9 and extracellular matrix metalloproteinase inducer (EMMPRIN) levels in relation to carotid atherosclerotic plaque characteristics. Methods-Carotid atherosclerotic plaques (nϭ150) were stained and analyzed for the presence of collagen, smooth muscle cell (SMC), and macrophages. Adjacent segments were used to isolate total protein to assess MMP-2 and MMP-9 activities and gelatin breakdown, MMP-8 activity, and EMMPRIN levels. Results-Macrophage-rich lesions revealed higher MMP-8 and MMP-9 activities, whereas SMC-rich lesions showed higher MMP-2 activity. The levels of less glycosylated EMMPRIN-45kD were higher in SMC-rich lesions and lower in macrophage-rich plaques. EMMPRIN-45kD was associated with MMP-2 levels, whereas EMMPRIN-58kD was related to MMP-9 levels. Conclusions-MMP-2, MMP-8, and MMP-9 activities differed among carotid plaque phenotypes. Different EMMPRIN glycosylation forms are associated with either MMP-2 or MMP-9 activity, which suggests that EMMPRIN glycosylation may play a role in MMP regulation and plaque destabilization. Key Words: atherosclerosis Ⅲ carotid arteries Ⅲ carotid artery plaque Ⅲ endarterectomy Ⅲ inflammation Ⅲ matrix metalloproteinases A therosclerosis is characterized by remodeling of the extracellular matrix and the accumulation of lipids and inflammatory cells. 1 Advanced stable atherosclerotic plaques are rich in collagen and smooth muscle cells (SMCs), whereas a large lipid core covered by a thin fibrous cap with a dense inflammatory infiltrate characterizes unstable and ruptured plaques. 2 Increased expressions of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, and 13 are found in macrophages and in SMCs covering the shoulder regions of atherosclerotic plaques. 3 Extracellular MMP inducer (EMMPRIN) stimulates the production of different MMPs. 4 EMMPRIN has been identified in human macrophage-rich atheroma. 5 However, the relation of EMMPRIN with plaque characteristics and MMP expression remains to be elucidated. In the present study, carotid endarterectomy plaque characteristics were associated with MMP-2, MMP-8, and MMP-9 activities and EMMPRIN expression levels. MethodsAthero-Express is an ongoing multicenter study in which carotid atherosclerotic specimen are obtained from patients undergoing endarterectomy. 6 Segments of the culprit lesion of each plaque were studied semiquantitatively for collagen content, SMCs, and macrophages and classified as no/minor or moderately/heavily stained. Moreover, an overall plaque phenotype was assigned to each lesion based on overall appearance.The adjacent segment was used to isolate total protein and MMP-2, MMP-8, and MMP-9. Total MMP activities were measured using the Biotrak activity assays RPN2631, RPN2635, and RPN2634, respectively (Amersham Biosciences). To determine pro-and active MMP-2 and MMP-9 levels in each plaque, zymography was performed as described elsewhere. 7 EMMPRIN expression levels were determined by Western blotting (sc-9753, Santa Cruz Bi...

Objective-Atherosclerotic cardiovascular disease is a major burden to health care. Because atherosclerosis is considered a systemic disease, we hypothesized that one single atherosclerotic plaque contains ample molecular information that predicts future cardiovascular events in all vascular territories. Methods and Results-AtheroExpress is a biobank collecting atherosclerotic lesions during surgery, with a 3-year follow-up. The composite primary outcome encompasses all cardiovascular events and interventions, eg, cardiovascular death, myocardial infarction, stroke, and endovascular interventions. A proteomics search identified osteopontin as a potential plaque biomarker. Patients undergoing carotid surgery (nϭ574) served as the cohort in which plaque osteopontin levels were examined in relation to their outcome during follow-up and was validated in a cohort of patients undergoing femoral endarterectomy (nϭ151). Comparing the highest quartile of carotid plaque osteopontin levels with quartile 1 showed a hazard ratio for the primary outcome of 3.8 (95% confidence interval, 2.6 -5.9). The outcome did not change after adjustment for plaque characteristics and traditional risk factors (hazard ratio, 3.5; 95% confidence interval, 2.0 -5.9). The femoral validation cohort showed a hazard ratio of 3.8 (95% confidence interval 2.0 to 7.4) comparing osteopontin levels in quartile 4 with quartile 1. Key Words: arterectomy Ⅲ atherosclerosis Ⅲ biomarker Ⅲ plaque A dvanced atherosclerotic cardiovascular disease continues to be a major burden to health care expenditures and requires exhaustive forms of medical treatment. A pressing need exists for prognostic biomarkers to identify high-risk patients for aggressive treatment. Conclusion-PlaqueProteins in the plasma are easily accessible and can serve as a surrogate measure of atherosclerotic disease progression, but existing circulating biomarkers do not provide an accurate value of predictive patient risk. 1,2 The main focus toward identifying patients with rapidly progressive advanced atherosclerotic disease is based on the known characteristics of the vulnerable or recently ruptured plaque with typically a large lipid core, thin fibrous cap, a high number of inflammatory cells, and thrombus. [3][4][5][6] The pathological definition of the vulnerable plaque is founded on cross-sectional studies. Subsequently, molecular and cellular features associated with the vulnerable plaque are considered potential diagnostic imaging markers for plaque rupture and plaque thrombosis. However, longitudinal studies supporting the predictive power of these pathological markers have not been executed, and information about the natural history of atherosclerotic disease is therefore incomplete. The systemic nature of atherosclerotic disease, however, is well-established 7-9 through histopathologic observations demonstrating that inflammation, 10 morphology, 11 and lipid content 12 correlate between different arterial segments within 1 individual. This gave rise to the hypothesis that local plaqu...