Plasma Matrix Metalloproteinase Levels Do Not Predict Tissue Levels in Abdominal Aortic Aneurysms Suitable for Elective Repair

Vascular ◽  
2008 ◽  
Vol 16 (5) ◽  
pp. 248-252 ◽  
Author(s):  
W. Richard W. Wilson ◽  
Edward C. Choke ◽  
Joseph Dawson ◽  
Ian M. Loftus ◽  
Matthew M. Thompson
Keyword(s):  
Matrix Metalloproteinase ◽  
Aortic Aneurysms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Levels ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Elective Repair ◽  
Circulating Levels ◽  
Aneurysm Diameter

The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) pathogenesis is well described. However, a clear role for the MMPs in disease prediction has not been established. The aim of this study was to determine if circulating levels of MMPs correlated with AAA diameter and with MMP concentrations within the aneurysm wall. Preoperative plasma samples and intraoperative infrarenal AAA sac biopsies were taken in a standard fashion from 31 patients undergoing elective repair. The concentrations of MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2 were quantified in plasma and aneurysm wall homogenates using enzyme-linked immunosorbent assay. Comparison used the Spearman correlation. There were no correlations between the paired plasma and aneurysm wall concentrations for any MMP or TIMP. Correlation between MMP-9 levels in the aneurysm wall and aneurysm diameter was negative ( r = −.42, p = .019). Other correlations between plasma and tissue levels with aneurysm diameter were nonsignificant.

scholarly journals Matrix Metalloproteinase-2 Isoforms Differ within the Aortic Wall of Ascending Aortic Aneurysms Associated with Bicuspid Aortic Valve

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ramona Schmitt ◽  
Anke Tscheuschler ◽  
Philipp Laschinski ◽  
Philipp Discher ◽  
Jana Fuchs ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Matrix Metalloproteinase ◽  
Bicuspid Aortic Valve ◽  
Aortic Wall ◽  
Aortic Aneurysms ◽  
Matrix Metalloproteinase 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Levels ◽  
Protein Levels ◽  
Underlying Pathogenesis

The pathogenesis of ascending thoracic aortic aneurysm (aTAA) is thought to differ between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV), and one of the causes is different hemodynamics. Influenced by hemodynamics, the tissue levels of proteins associated with aTAA might differ between aTAAs with BAV and TAV and between different localities within the aortic wall. We therefore analyzed aTAA tissue levels of MMP-2 (matrix metalloproteinase-2) isoforms (Pro-MMP-2, active MMP-2, and total MMP-2) and tissue levels of MMP-14, TIMP-2 (tissue inhibitor of metalloproteinase-2), MMP-9, and TIMP-1 in 19 patients with BAV and 23 patients with TAV via gelatin zymography and enzyme-linked immunosorbent assay (ELISA), respectively. TAV and BAV groups’ protein levels did not differ significantly. Whereas the TAV group exhibited no significant differences in protein levels between the aneurysm’s anterior and posterior parts, the BAV group revealed significantly higher levels of Pro-MMP-2, total MMP-2, and TIMP-2 in the aneurysm’s posterior parts (mean Pro-MMP-2 200.52 arbitrary units (AU) versus 161.12 AU, p=0.007; mean total MMP-2 235.22 AU versus 193.68 AU, p=0.002; mean TIMP-2 26.90 ng/ml versus 25.36 ng/ml, p=0.009), whereas the other proteins did not differ significantly within the aortic wall. Thus, MMPs are distributed more heterogeneously within the aortic wall of aTAAs associated with BAV than in those associated with TAV, which is a new aspect for understanding the underlying pathogenesis. This heterogeneous protein level distribution might be attributable to differences in the underlying pathogenesis, especially hemodynamics. This result is important for further studies as it will be essential to specify the location of samples to ensure data comparability regarding the main goals of understanding the pathogenesis of aTAA, optimizing treatments, and establishing a screening method for its potentially deadly complications.

Endotension Distribution and the Role of Thrombus following Endovascular AAA Exclusion

2002 ◽  
Vol 9 (5) ◽  
pp. 639-651 ◽  
Author(s):  
John P. Pacanowski ◽  
Scott L. Stevens ◽  
Michael B. Freeman ◽  
Robert S. Dieter ◽  
Lance A. Klosterman ◽  
...  
Keyword(s):  
Stent Graft ◽  
Statistical Significance ◽  
Aortic Aneurysms ◽  
Similar Degree ◽  
Pump System ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Before And After ◽  
Fibrin Thrombus

Purpose: To determine the pattern of strain and pressure transmitted to an aortic aneurysm wall before and after endovascular exclusion and to evaluate the role of sac thrombus on the conduction of pressure and wall strain. Methods: Three canine thoracic aortas were used to create abdominal aortic aneurysms (AAA). The segments were placed on a pulsatile pump system, and 8 strain transducers were positioned in the aneurysm sac. Baseline strain/pressure (S/P) was recorded in 1 animal, then the AAA was excluded with a stent-graft. Thrombin was injected into the sac, and strain/pressure was recorded at 7 systemic pressures (35 to 120 mmHg) over 6 hours. The thrombus was replaced with fibrin glue, and S/P was recorded over 4 hours. Additional trials using whole and 50% diluted unclotted blood were performed prior to sac thrombosis. Computed tomography and angiography were performed before and after aneurysm exclusion. Results: Pressure transmitted to the aneurysm wall decreased following stent-graft placement (p≤0.001). Strain/pressure was not distributed evenly in the sac (p≤0.05), and varying systemic pressures did not affect this distribution. Pressures near the stent-graft were higher than those laterally (p≤0.001) in all trials with interposed fresh thrombus and fibrin thrombus. The fibrin group had elevated baseline measurements, but correction for the elevated values did not influence the statistical significance (p≤0.001). Blood and fibrin thrombus reduced transmitted wall pressure to a similar degree. Overall S/P in the fluid-filled nonclotted sac was significantly lower (p≤0.001) than in the thrombus groups. Conclusions: Endovascular AAA exclusion reduced strain and pressure conducted to the aneurysm wall, and the distribution of transmitted pressure in the excluded sac without endoleak differed regardless of the sac contents. Fresh thrombus reduced transmitted S/P in all trials at all systemic pressures, as did fibrin thrombus but in a less predictable fashion.

Abstract 1031: First Human Experiments: Aggressive Statin Therapy Reduced Key Inflammatory Factors including c-Jun N-terminal kinase (JNK) and Dendritic Cell and Matrix Metalloproteinase Expression in Human Abdominal Aortic Aneurysmal Wall

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Kan Kajimoto ◽  
Katsumi Miyauchi ◽  
Kazunori Shimada ◽  
Takatoshi Kasai ◽  
Yuko Kojima ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Aortic Aneurysms ◽  
Inflammatory Factors ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
Atorvastatin Group ◽  
Aneurysm Wall ◽  
Abdominal Aortic

Abdominal aortic aneurysms (AAA) accumulate feature of a chronic inflammatory disorder and irreversible destruction connective tissue. Recent experimental study demonstrated that c-Jun N terminal kinase (JNK) was a proximal signaling molecule in the pathogenesis of AAA and vascular dendritic cells (DC) were the key molecular in inflammatory reaction and the degradation of the extracellular matrix. Statins can inhibit cell proliferation and vascular inflammation, which might contribute to prevent AAA progrssion. But supporting clinical data from human studies are lacking. We hypothesized that atorvastatin might inhibit JNK and DC, resulting in suppression of inflammatory cells and matrix metalloproteinase (MMPs) in human tissue of AAA. Methods : Patients with AAA were randomized to the atorvastatin (20 mg/day, 10 patients) group or control (10 patients) group. After treatment of 4 weeks, patients underwent abdominal aorta replacement, tissue specimens were obtained, and the tissue composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Results :Atorvastatin significantly reduced JNK and DC expression (46% and 72%) compared to control. T cells, macrophages (60%, 72%, P< 0.05), and MMP-2 and MMP-9 immunoreactivity (47%, 43%, P< 0.05) were also suppressed in atorvastatin group. However, tissue expression of metalloproteinase 1 (TIMP-1) immunoreactivity and a collagen content by sirius red staining were similar in both groups. In atorvastatin group, serum LDL-C level was significantly decreased by 40%. Conclusion: Atorvastatin treatment reduced the JNK expression and DE, resulting in inflammatory cells content and the expression of MMPs in human abdominal aortic aneurysm wall.

Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice

2015 ◽  
Vol 93 (8) ◽  
pp. 641-648 ◽  
Author(s):  
Azza Ramadan ◽  
Mark D. Wheatcroft ◽  
Adrian Quan ◽  
Krishna K. Singh ◽  
Fina Lovren ◽  
...  
Keyword(s):  
Natural History ◽  
Thrombus Formation ◽  
Aortic Aneurysms ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Suprarenal Aorta ◽  
History Of ◽  
Categorical Distribution

Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE−/− mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)–1·day–1, by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation.

scholarly journals The Role of Geometric Parameters in the Prediction of Abdominal Aortic Aneurysm Wall Stress

2010 ◽  
Vol 39 (1) ◽  
pp. 42-48 ◽  
Author(s):  
E. Georgakarakos ◽  
C.V. Ioannou ◽  
Y. Kamarianakis ◽  
Y. Papaharilaou ◽  
T. Kostas ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Wall Stress ◽  
Geometric Parameters ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Abdominal Aortic Aneurysm Wall
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