D-Dimers and MPO Are No Suitable Biomarkers for Application in Abdominal Aortic Aneurysm (AAA) Surveillance in a Real-World Setting of Vascular Surgery Patients.

There is currently no clinically valid biomarker for predicting the growth and prognosis of abdominal aortic aneurysms (AAA). The most promising candidates with the highest diagnostic values are plasma D-dimers and markers of activated neutrophils, i.e.

Histopathological Characterization of Abdominal Aortic Aneurysms from Patients with Multiple Aneurysms Compared to Patients with a Single Abdominal Aortic Aneurysm.

The aim of this study was to investigate histopathological differences in abdominal aortic aneurysms (AAAs) between patients with multiple and single arterial aneurysms, as we suspect that there are different underlying mechanisms in aneurysm formation. Analysis was based on a previous retrospective study on patients with multiple arterial aneurysms (; defined as at least four, = 143) and a single AAA (, = 972) who were admitted to our hospital for treatment between 2006 and 2016. Available paraffin-embedded AAA wall specimens were derived from the Vascular Biomaterial Bank Heidelberg (, = 12 vs.

Mitochondrial Dysfunction and Increased DNA Damage in Vascular Smooth Muscle Cells of Abdominal Aortic Aneurysm (AAA-SMC).

There is increasing evidence for enhanced oxidative stress in the vascular wall of abdominal aortic aneurysms (AAA). Mitochondrial damage and dysfunction are hypothesized to be actors in altered production of reactive oxygen species (ROS) and oxidative stress. However, the role of mitochondria and oxidative stress in vascular remodelling and progression of AAA remains uncertain.

Multiple Arterial Dissections and Connective Tissue Abnormalities.

Background: Although patients with multiple arterial dissections in distinct arterial regions rarely present with known connective tissue syndromes, we hypothesized that mild connective tissue abnormalities are common findings in these patients.

Methods: From a consecutive register of 322 patients with cervical artery dissection (CeAD), we identified and analyzed 4 patients with a history of additional dissections in other vascular beds. In three patients, dermal connective tissue was examined by electron microscopy.

Inflammasome Targeted Therapy as Novel Treatment Option for Aortic Aneurysms and Dissections: A Systematic Review of the Preclinical Evidence.

Both aortic aneurysm and dissection are life threatening pathologies. In the lack of a conservative medical treatment, the only therapy consists of modifying cardiovascular risk factors and either surgical or endovascular treatment. Like many other cardiovascular diseases, in particular atherosclerosis, aortic aneurysm and dissection have a strong inflammatory phenotype.

Inflammasomes in the Pathophysiology of Aortic Disease.

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation.

The C57Bl/6J mouse strain is more susceptible to angiotensin II-induced aortic aneurysm formation than C57Bl/6N.

Background And Aims: Genetic variations between C57Bl/6 mouse substrains are highly relevant to the investigation of cardiovascular disease. We here assessed whether these variations have an impact on the incidence of abdominal aortic aneurysms (AAA) in C57Bl/6J and 6 N mice.

Methods: AAA were induced by subcutaneous infusion of 1500 ng/kg*min Angiotensin-II for four weeks in six-month-old male CB57Bl/6J and 6N mice.

Deficiency in Aim2 affects viability and calcification of vascular smooth muscle cells from murine aortas and angiotensin-II induced aortic aneurysms.

Background: Phenotypic transformation of vascular smooth muscle cells is a key element in vascular remodeling and aortic aneurysm growth. Previously, deletion of several inflammasome components decreased formation of aortic aneurysm (AA) in the Angiotensin II (AngII) -induced mouse model. We hypothesized that the inflammasome sensor Absent in melanoma 2 (Aim2) might affect the phenotype of vascular smooth muscle cells (VSMC), thereby reducing AA formation.

[Development of arteriosclerosis].

Arteriosclerosis is the general term for a group of arterial vascular diseases characterized by arterial wall thickening and loss of elasticity, which are caused by different biological processes. The most commonly used classification defines four distinct histopathological types: arteriolosclerosis, medial sclerosis, fibromuscular intimal hyperplasia and atherosclerosis. The pathobiological remodeling of the arterial wall essentially represents different repair responses of vascular cells to molecular stress factors and microlesions.

Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression.

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. The present extended immunohistochemistry study aimed to characterize inflammation in AAA and aortic control samples. In specific, the composition of the infiltrating immune cells and the expression of five inflammasome components in these immune cells were evaluated, in order to characterize their role in AAA development.

Necrotic cell debris induces a NF-κB-driven inflammasome response in vascular smooth muscle cells derived from abdominal aortic aneurysms (AAA-SMC).

Abdominal aortic aneurysm (AAA) is a multi-factorial progressive vascular disease with life-threatening complications. Increasing evidence suggests that smooth muscle cell (SMC) dysfunction and cell death contribute to dilatation and rupture of the aorta by inducing an inflammatory response. The exact mechanism of this response however, is incompletely understood.

AIM2 levels and DNA-triggered inflammasome response are increased in peripheral leukocytes of patients with abdominal aortic aneurysm.

Objective And Design: Abdominal aortic aneurysm (AAA) is heavily infiltrated with leukocytes, expressing the DNA sensor absent in melanoma 2 (AIM2) and other inflammasome components.

Methods: Using multicolour flow cytometry, we here compared the expression of the inflammasome components AIM2, NLRP3, and ASC in different peripheral immune cells derived from AAA patients with those from non-AAA patients in a case-control study. In parallel, peripheral blood mononuclear cells (PBMC) of AAA patients and controls were stimulated in vitro with poly-dA:dT or lipopolysaccharide (LPS) to analyze inflammasome activation.

Gene Expression Profiling in Abdominal Aortic Aneurysms After Finite Element Rupture Risk Assessment.

Purpose: To investigate the association between local biomechanical rupture risk calculations from finite element analysis (FEA) and whole-genome profiling of the abdominal aortic aneurysm (AAA) wall to determine if AAA wall regions with highest and lowest estimated rupture risk show different gene expression patterns.

Methods: Six patients (mean age 74 years; all men) scheduled for open surgery to treat asymptomatic AAAs (mean diameter 55.2±3.

Reduced glyoxalase 1 activity in carotid artery plaques of nondiabetic patients with increased hemoglobin A1c level.

Objective: Glyoxalase 1 (GLO1) is ubiquitously expressed in the cytosol of the cell and is the major opponent against the reactive metabolite methylglyoxal, which is involved in the development of atherosclerosis. Nondiabetic individuals with an increased hemoglobin A1c (HbA1c) level are at higher risk for development of cardiovascular diseases. As such, this study investigated whether there was an association between reduced GLO1 activity in atherosclerotic lesions of nondiabetic patients with an increased HbA1c level.

Sex- and disease-specific inflammasome signatures in circulating blood leukocytes of patients with abdominal aortic aneurysm.

Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex.

A Glyoxalase-1 Knockdown Does Not Have Major Short Term Effects on Energy Expenditure and Atherosclerosis in Mice.

Objective. Glyoxalase-1 is an enzyme detoxifying methylglyoxal (MG). MG is a potent precursor of advanced glycation endproducts which are regarded to be a key player in micro- and macrovascular damage.

Gene expression of inflammasome components in peripheral blood mononuclear cells (PBMC) of vascular patients increases with age.

Background: Chronic low-grade inflammation is considered a driver of many age-related disorders, including vascular diseases (inflammaging). Inhibition of autophagic capacity with ageing was postulated to generate a pro-inflammatory condition via activation of inflammasomes, a group of Interleukin-1 activating intracellular multi-protein complexes. We thus investigated gene expression of inflammasome components in PBMC of 77 vascular patients (age 22-82) in association with age.

Coding Microsatellite Frameshift Mutations Accumulate in Atherosclerotic Carotid Artery Lesions: Evaluation of 26 Cases and Literature Review.

Somatic DNA alterations are known to occur in atherosclerotic carotid artery lesions; however, their significance is unknown. The accumulation of microsatellite mutations in coding DNA regions may reflect a deficiency of the DNA mismatch repair (MMR) system. Alternatively, accumulation of these coding microsatellite mutations may indicate that they contribute to the pathology.

Finite element analysis of abdominal aortic aneurysms: predicted rupture risk correlates with aortic wall histology in individual patients.

Purpose: To evaluate a finite element analysis (FEA) model as a predictive tool for abdominal aortic aneurysm (AAA) rupture risk assessment.

Methods: FEA of asymptomatic infrarenal AAAs in 15 men (mean age 72 years) was performed preoperatively using semiautomatic finite element analysis software (A4clinics) to calculate peak wall stress (PWS) and regions of highest and lowest rupture risk index (RRI). The areas of high and low RRI identified on the preoperative FEA were sampled during open surgery; aortic wall specimens were prepared for histological analysis.

Gender difference in glyoxalase 1 activity of atherosclerotic carotid artery lesions.

Objective: Age and gender are two factors that determine the risk of atherosclerosis. The latter effect is only partly understood. Dicarbonyls, in particular methylglyoxal, participate in the development of atherosclerosis, and their major detoxification route is the enzyme glyoxalase 1 (GLO1), which is known to decrease during aging.

Lack of Absent in Melanoma 2 (AIM2) expression in tumor cells is closely associated with poor survival in colorectal cancer patients.

Functional studies on colorectal cancer cells indicated a protective role of the interferon-inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5-year follow-up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers.

Glyoxalase I (Glo1) and its metabolites in vascular disease.

Glo1 (glyxoalase I) is a cytosolic protein expressed in all mammalian cells. Its physiological function is the detoxification of MG (methylglyoxal), which is a potent precursor of AGEs (advanced glycation end-products). Although the impact of AGEs on different forms of vascular diseases has been intensively investigated, the evidence for the involvement of Glo1 and MG is still scarce.