ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis.
Eva BengtssonKarin HultmanPontus DunérGiuseppe AsciuttoPeter AlmgrenMarju Orho-MelanderOlle MelanderJan NillsonAnna Hultgårdh-NilssonIsabel GonçalvesPublished in: Scientific reports (2017)
Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.
Keyphrases
- coronary artery disease
- cardiovascular events
- end stage renal disease
- smooth muscle
- endothelial cells
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- cardiovascular disease
- coronary artery bypass grafting
- prognostic factors
- electronic health record
- gene expression
- percutaneous coronary intervention
- machine learning
- big data
- patients undergoing
- heart failure
- stem cells
- physical activity
- aortic valve
- high resolution
- binding protein
- copy number
- drug induced
- depressive symptoms
- dna methylation
- bone marrow
- human health
- aortic stenosis
- transcatheter aortic valve replacement