scholarly journals Thrombospondin-1 contributes to slower aortic aneurysm growth by inhibiting maladaptive remodeling of extracellular matrix

2017 ◽  
Vol 131 (12) ◽  
pp. 1283-1285 ◽  
Author(s):  
Mamoru Satoh ◽  
Takahito Nasu ◽  
Takuya Osaki ◽  
Sho Hitomi
Keyword(s):  
Extracellular Matrix ◽  
Aortic Aneurysm ◽  
Recent Work ◽  
Mouse Models ◽  
Causal Relation ◽  
Clinical Science ◽  
Thrombospondin 1 ◽  
Aneurysm Growth ◽  
Remodeling Of Extracellular Matrix

In this issue of Clinical Science, Krishna and colleagues describe recent work on thrombospondin-1 (TSP-1) maturation and its association with slower growth of aortic aneurysm in TSP-1 knockdown mouse models. The authors conclude that TSP-1 deficiency promotes maladaptive remodeling of the extracellular matrix (ECM) leading to accelerated aortic aneurysm progression. We comment on a causal relation between TSP-1 and the progression of aortic aneurysm.

scholarly journals Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm

2020 ◽  
Vol 318 (3) ◽  
pp. H652-H670 ◽  
Author(s):  
Bo Liu ◽  
David J. Granville ◽  
Jonathan Golledge ◽  
Zamaneh Kassiri
Keyword(s):  
Extracellular Matrix ◽  
Aortic Aneurysm ◽  
Aortic Rupture ◽  
Wall Structure ◽  
Pharmacological Treatments ◽  
Cellular Functions ◽  
The Past ◽  
Abdominal Aortic ◽  
Aneurysm Growth ◽  
Asymptomatic Disease

Aortic aneurysm is a permanent focal dilation of the aorta. It is usually an asymptomatic disease but can lead to sudden death due to aortic rupture. Aortic aneurysm-related mortalities are estimated at ∼200,000 deaths per year worldwide. Because no pharmacological treatment has been found to be effective so far, surgical repair remains the only treatment for aortic aneurysm. Aortic aneurysm results from changes in the aortic wall structure due to loss of smooth muscle cells and degradation of the extracellular matrix and can form in different regions of the aorta. Research over the past decade has identified novel contributors to aneurysm formation and progression. The present review provides an overview of cellular and noncellular factors as well as enzymes that process extracellular matrix and regulate cellular functions (e.g., matrix metalloproteinases, granzymes, and cathepsins) in the context of aneurysm pathogenesis. An update of clinical trials focusing on therapeutic strategies to slow abdominal aortic aneurysm growth and efforts underway to develop effective pharmacological treatments is also provided.

scholarly journals 30143 Asymptomatic Thoracic Aortic Aneurysm Growth Rates and Predicting Factors: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-2
Author(s):  
Matthew Henry ◽  
Pieter Van Bakelrk MacEachernrion Hoffman Bowman ◽  
Kim Eagle ◽  
Himanshu ◽  
Patel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Aortic Aneurysm ◽  
Growth Rates ◽  
Thoracic Aortic Aneurysm ◽  
Meta Analysis ◽  
Predicting Factors ◽  
Aneurysm Growth

scholarly journals Complement Factor C5a Is Increased in Blood of Patients with Abdominal Aortic Aneurysm and Has Prognostic Potential for Aneurysm Growth

2020 ◽  
Author(s):  
Branislav Zagrapan ◽  
Wolf Eilenberg ◽  
Andreas Scheuba ◽  
Johannes Klopf ◽  
Annika Brandau ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Leukotriene B4 ◽  
Complement Factor ◽  
Diagnosis And Prognosis ◽  
Abdominal Aortic ◽  
Aneurysm Growth ◽  
Log Linear

AbstractIn this observational case-control study, circulating levels of complement factors C3a and C5a and leukotriene B4 (LTB4) were analysed in abdominal aortic aneurysm (AAA) patients regarding their association with diagnosis and prognosis. Serum C5a was significantly raised in AAA patients compared to healthy controls—median 84.5 ng/ml (IQR = 37.5 ng/ml) vs. 67.7 ng/ml (IQR = 26.2 ng/ml), p = 0.007—but was not elevated in patients with athero-occlusive disease. Serum C5a levels correlated significantly with the increase in maximum AAA diameter over the following 6 months (r = 0.319, p = 0.021). The median growth in the lowest quartile of C5a (< 70 ng/ml) was 50% less compared to the highest C5a quartile (> 101 ng/ml): 1.0 mm/6 months (IQR = 0.8 mm) vs. 2.0 mm/6 months (IQR = 1.5 mm), p = 0.014. A log-linear mixed model predicted AAA expansion based on current diameter and C5a level. To our knowledge, this is the first study linking complement activation, in particular C5a serum level, with AAA progression. Graphical Abstract

Abstract 297: Segmental Aortic Stiffening is a Mechanism Driving Early Abdominal Aortic Aneurysm Pathogenesis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Uwe Raaz ◽  
Alexander M Zöllner ◽  
Ryuji Toh ◽  
Futoshi Nakagami ◽  
Isabel N Schellinger ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Wall ◽  
Ex Vivo ◽  
Wall Stress ◽  
Finite Elements Analysis ◽  
External Application ◽  
Abdominal Aortic ◽  
Aneurysm Growth ◽  
Aortic Stiffening

Stiffening of the aortic wall is a phenomenon consistently observed in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined. Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening (SAS) precedes aneurysm growth. Finite elements analysis (FEA)-based wall stress calculations reveal that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with reduced segmental stiffness of the AAA-prone aorta (due to equalized stiffness in adjacent aortic segments), reduced axial wall stress, decreased production of reactive oxygen species (ROS), attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, as well as attenuated apoptosis within the aortic wall. Cyclic pressurization of stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix (ECM) remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening. The present study introduces the novel concept of segmental aortic stiffening (SAS) as an early pathomechanism generating aortic wall stress and thereby triggering AAA growth. Therefore monitoring SAS by ultrasound might help to better identify patients at risk for AAA disease and better predict the susceptibility of small AAA to further growth. Moreover our results suggest that interventional mechanical stiffening of the AAA-adjacent aorta may be further tested as a novel treatment option to limit early AAA growth.

scholarly journals A High-Throughput Workflow to Study Remodeling of Extracellular Matrix-Based Microtissues

2019 ◽  
Vol 25 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Alexandra L. Crampton ◽  
Katherine A. Cummins ◽  
David K. Wood
Keyword(s):  
Extracellular Matrix ◽  
High Throughput ◽  
Remodeling Of Extracellular Matrix
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