2013
DOI: 10.1161/circresaha.113.301498
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Thoracic Aortic Aneurysm Frequency and Dissection Are Associated With Fibrillin-1 Fragment Concentrations in Circulation

Abstract: Rationale: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome.Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA.Objective: Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection. Methods and Results:

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Cited by 57 publications
(46 citation statements)
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“…Untreated cell cultures were used as a control. Medium was collected and a modified sandwich ELISA was used to quantitate secreted fibrillin-1 in cell culture medium as described previously [30]. Two antibody pairs consisting of a biotinylated (B) capture antibody and an alkaline phosphatase (AP)-conjugated detector antibody that recognize fibrillin-1 were used in this modified sandwich ELISA, B15-AP201 and B15-AP78.…”
Section: Methodsmentioning
confidence: 99%
“…Untreated cell cultures were used as a control. Medium was collected and a modified sandwich ELISA was used to quantitate secreted fibrillin-1 in cell culture medium as described previously [30]. Two antibody pairs consisting of a biotinylated (B) capture antibody and an alkaline phosphatase (AP)-conjugated detector antibody that recognize fibrillin-1 were used in this modified sandwich ELISA, B15-AP201 and B15-AP78.…”
Section: Methodsmentioning
confidence: 99%
“…Accordingly, treatment with a miR-29b oligonucleotide inhibitor prevented early formation of aneurysms. 41) Finally, plasma levels of TGF-β, 26) fibrillin-1 fragments, 42) macrophage colony stimulating factor (M-CSF), 21) and oxidative stress indicators 43) have been reported as useful biomarkers for disease progression in humans and animal models. C1039G/+ mice showed significant increases in activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and mitogen-activated protein kinase kinase 1 (MEK1), which is the upstream activator of ERK1/2.…”
Section: ;Tgfb2mentioning
confidence: 99%
“…When plasma of 1091 patients with TAA (N10% due to MFS) was analyzed for indication of microfibril fragmentation, fibrillin-1 fragments were found to be circulating in large amounts, especially in those who had undergone aortic dissections [60]. Cells treated with fibrillin-1 fragments containing the arginineglycine-aspartic acid (RGD) integrin-binding motif or elastin-bindingprotein GxxPG consensus sequence, showed increased MMP levels [61,62].…”
Section: Other Variables In Mfsmentioning
confidence: 99%
“…Long-term monitoring of aortic dilation in conjunction with other developing complications will continue to be part of routine follow-up for MFS patients. Availability of circulating biomarkers for MFS would prove helpful in such patients, however potentially useful markers such as circulating fibrillin-1 fragments and TGF-β1 may similarly be found in overlapping syndromes [60,76]. Efforts to identify novel and unique targets such as MMP profiles [47], inflammatory pathways [65] and microRNA signatures (NCT02213484; www.…”
Section: Cellular Model For Mfsmentioning
confidence: 99%