Dataset Information

MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms.

ABSTRACT:

Objective

The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress.

Methods

Serum and aortic tissue from n = 24 patients and serum from n = 19 healthy controls was analyzed by ELISA and gelatin zymography. 24 patients had ascending aortic aneurysms, 10 of them also had aortic root aneurysms. Three patients had normally functioning valves, 12 had regurgitation alone, eight had regurgitation and stenosis and one had only stenosis. Patients had bicuspid and tricuspid aortic valves (9/15). Serum samples were taken preoperatively, and the aortic wall specimen collected during surgical aortic repair.

Results

Pro-MMP-2 was identified in all serum and tissue samples. Pro-MMP-2 was detected in all tissue and serum samples from patients with ascending aortic/aortic root aneurysms, irrespective of valve morphology or other clinical parameters and in serum from healthy controls. We also identified active MMP-2 in all tissue samples from patients with ascending aortic/aortic root aneurysms. None of the analyzed serum samples revealed signals relatable to active MMP-2. No correlation between aortic tissue total MMP-2 or tissue pro-MMP-2 or tissue active MMP-2 and serum MMP-2 was found and tissue MMP-2/pro-MMP-2/active MMP-2 did not correlate with aortic diameter. This evidence shows that pro-MMP-2 is the predominant MMP-2 species in serum of patients and healthy individuals and in aneurysmatic aortic tissue, irrespective of aortic valve configuration. Active MMP-2 species are either not released into systemic circulation or not detectable in serum. There is no reliable connection between aortic tissue-and serum MMP-2 isoforms, nor any indication that pro-MMP-2 functions as a common marker of high aortic wall stress.

SUBMITTER: Tscheuschler A

PROVIDER: S-EPMC5089694 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms.

Tscheuschler Anke A Meffert Philipp P Beyersdorf Friedhelm F Heilmann Claudia C Kocher Nadja N Uffelmann Xenia X Discher Philipp P Siepe Matthias M Kari Fabian A FA

PloS one 20161101 11

<h4>Objective</h4>The need for biological markers of aortic wall stress and risk of rupture or dissection of ascending aortic aneurysms is obvious. To date, wall stress cannot be related to a certain biological marker. We analyzed aortic tissue and serum for the presence of different MMP-2 isoforms to find a connection between serum and tissue MMP-2 and to evaluate the potential of different MMP-2 isoforms as markers of high wall stress.<h4>Methods</h4>Serum and aortic tissue from n = 24 patient ...[more]

PMID: 27802285

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Project description:ObjectivesThe study objective was to evaluate the aortic wall stress and root dilatation before and after the novel V-shape surgery for the treatment of ascending aortic aneurysms and root ectasia.MethodsClinical cardiac computed tomography images were obtained for 14 patients [median age, 65 years (range, 33-78); 10 (71%) males] who underwent the V-shape surgery. For 10 of the 14 patients, the computed tomography images of the whole aorta pre- and post-surgery were available, and finite element simulations were performed to obtain the stress distributions of the aortic wall at pre- and post-surgery states. For 6 of the 14 patients, the computed tomography images of the aortic root were available at 2 follow-up time points post-surgery (Post 1, within 4 months after surgery and Post 2, about 20-52 months from Post 1). We analysed the root dilatation post-surgery using change of the effective diameter of the root at the two time points and investigated the relationship between root wall stress and root dilatation.ResultsThe mean and peak max-principal stresses of the aortic root exhibit a significant reduction, P=0.002 between pre- and post-surgery for both root mean stress (median among the 10 patients presurgery, 285.46 kPa; post-surgery, 199.46 kPa) and root peak stress (median presurgery, 466.66 kPa; post-surgery, 342.40 kPa). The mean and peak max-principal stresses of the ascending aorta also decrease significantly from pre- to post-surgery, with P=0.004 for the mean value (median presurgery, 296.48 kPa; post-surgery, 183.87 kPa), and P=0.002 for the peak value (median presurgery, 449.73 kPa; post-surgery, 282.89 kPa), respectively. The aortic root diameter after the surgery has an average dilatation of 5.01% in total and 2.15%/year. Larger root stress results in larger root dilatation.ConclusionsThis study marks the first biomechanical analysis of the novel V-shape surgery. The study has demonstrated significant reduction in wall stress of the aortic root repaired by the surgery. The root was able to dilate mildly post-surgery. Wall stress could be a critical factor for the dilatation since larger root stress results in larger root dilatation. The dilated aortic root within 4 years after surgery is still much smaller than that of presurgery.

Project description:BackgroundThoracic Aortic Aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threatening vascular disorder due to the risk of aortic dissection and rupture. There is an urgent need to identify blood-borne biomarkers for the early detection of TAA. The goal of the present study was to identify potential protein biomarkers associated with TAAs, using proteomic analysis of aortic tissue and plasma samples.MethodsExtracted proteins from 14 aneurysmal and 12 non-aneurysmal thoracic aortic tissue specimens as well as plasma samples from six TAA patients collected pre-and postoperatively and six healthy controls (HC), were analyzed by liquid chromatography-tandem mass spectrometry. Proteomic data were further processed and following filtering criteria, one protein was selected for verification and validation in a larger cohort of patients and controls using a targeted quantitative proteomic approach and enzyme-linked immunosorbent assay, respectively.ResultsA total of 1593 and 363 differentially expressed proteins were identified in tissue and plasma samples, respectively. Pathway enrichment analysis on the differentially expressed proteins revealed a number of dysregulated molecular pathways that might be implicated in aneurysm pathology including complement and coagulation cascades, focal adhesion, and extracellular matrix receptor interaction pathways. Alpha-2-HS glycoprotein (AHSG) was selected for further verification in 36 TAA and 21 HC plasma samples using targeted quantitative proteomic approach. The results showed a significantly decreased concentration of AHSG (p = 0.0002) in the preoperative plasma samples compared with HC samples. Further analyses using a larger validation dataset revealed that AHSG protein levels were significantly lower (p = 0.03) compared with HC. Logistic regression analysis on the validation dataset revealed males, advanced age, hypertension and hyperlipidaemia as significant risk factors for TAA.ConclusionAHSG concentrations distinguish plasma samples derived from TAA patients and controls. The findings of this study suggest that AHSG may be a potential biomarker for TAA that could lead to better diagnostic capabilities.

Project description:ObjectivesThis study aims to characterize the material properties of ascending thoracic aortic aneurysmal tissue, using regional biomechanical assessment of both tensile and dissection propagation peel strength.MethodsThirty-four aneurysm specimens (proximal thoracic aorta) were harvested en-bloc from patients undergoing surgery for aneurysm replacement. Specimens were processed into regional samples of similar shapes covering the whole aneurysm isosurface, according to a structured protocol, in both orientations (longitudinal and circumferential). Thickness mapping, uniaxial tensile and peel tests were conducted, enabling calculation of the following parameters: true stress/strain, tangential modulus, tensile strength, peeling force and dissection energy. Two constitutive material models were used (hyperelastic models of Delfino and Ogden) to fit the data. A circumferential strip of tissue was also obtained for computational histology [regional quantification of (i) elastin, (ii) collagen and (iii) smooth muscle cells].ResultsThe aortic wall was thinner on the outer curve (2.21, standard deviation (SD) 0.4 mm vs inner curve 2.50, SD 0.12 mm). Advanced patient age and higher pulse wave velocity (externally measured) were predictors of increased aortic wall thickness. Tensile strength was higher in the circumferential versus longitudinal direction when analysed according to anatomical regions. Both peel force (35.5, 22 N/m) and dissection energy (88.5, 69 J/m2) were on average lowest at the outer curve of the aneurysm in the longitudinal orientation. Delfino and Ogden model constants varied throughout anatomical regions, with the outer curve being associated a higher ɑ constant (Delfino) and lower µ1 constant (Ogden) (P < 0.05) indicating increased stiffness. Histologically, collagen abundance was significantly related to circumferential and longitudinal strength (P= 0.010), whilst smooth muscle cell count had no relation with any mechanical property (P > 0.05).ConclusionsOur results suggest that the outer aortic curve is more prone to dissection propagation and perhaps less prone to rupture than the inner aortic curve. This strengthens the notion of disease heterogeneity in ascending thoracic aortic aneurysms and has implications for the pathogenesis of aortic dissection.

Project description:ObjectiveGuidelines for repair of bicuspid aortic valve-associated ascending thoracic aortic aneurysms have been changing, most recently to the same criteria as tricuspid aortic valve-ascending thoracic aortic aneurysms. Rupture/dissection occurs when wall stress exceeds wall strength. Recent studies suggest similar strength of bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms; thus, comparative wall stress may better predict dissection in bicuspid aortic valve versus tricuspid aortic valve-ascending thoracic aortic aneurysms. Our aim was to determine whether bicuspid aortic valve-ascending thoracic aortic aneurysms had higher wall stresses than their tricuspid aortic valve counterparts.MethodsPatients with bicuspid aortic valve- and tricuspid aortic valve-ascending thoracic aortic aneurysms (bicuspid aortic valve = 17, tricuspid aortic valve = 19) greater than 4.5 cm underwent electrocardiogram-gated computed tomography angiography. Patient-specific 3-dimensional geometry was reconstructed and loaded to systemic pressure after accounting for prestress geometry. Finite element analyses were performed using the LS-DYNA solver (LSTC Inc, Livermore, Calif) with user-defined fiber-embedded material model to determine ascending thoracic aortic aneurysm wall stress.ResultsBicuspid aortic valve-ascending thoracic aortic aneurysms 99th-percentile longitudinal stresses were 280 kPa versus 242 kPa (P = .028) for tricuspid aortic valve-ascending thoracic aortic aneurysms in systole. These stresses did not correlate to diameter for bicuspid aortic valve-ascending thoracic aortic aneurysms (r = -0.004) but had better correlation to tricuspid aortic valve-ascending thoracic aortic aneurysms diameter (r = 0.677). Longitudinal stresses on sinotubular junction were significantly higher in bicuspid aortic valve-ascending thoracic aortic aneurysms than in tricuspid aortic valve-ascending thoracic aortic aneurysms (405 vs 329 kPa, P = .023). Bicuspid aortic valve-ascending thoracic aortic aneurysm 99th-percentile circumferential stresses were 548 kPa versus 462 kPa (P = .033) for tricuspid aortic valve-ascending thoracic aortic aneurysms, which also did not correlate to bicuspid aortic valve-ascending thoracic aortic aneurysm diameter (r = 0.007).ConclusionsCircumferential and longitudinal stresses were greater in bicuspid aortic valve- than tricuspid aortic valve-ascending thoracic aortic aneurysms and were more pronounced in the sinotubular junction. Peak wall stress did not correlate with bicuspid aortic valve-ascending thoracic aortic aneurysm diameter, suggesting diameter alone in this population may be a poor predictor of dissection risk. Our results highlight the need for patient-specific aneurysm wall stress analysis for accurate dissection risk prediction.

Dataset Information

MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms.

Objective

Methods

Results

Publications

MMP-2 Isoforms in Aortic Tissue and Serum of Patients with Ascending Aortic Aneurysms and Aortic Root Aneurysms.

Similar Datasets

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