elastin and Carotid-Stenosis

The purpose of this study was to analyze the association between morphological characteristics of human carotid plaques and patient's sex, age, and history of neurological symptoms.. The study included 763 atherosclerotic plaques from patients treated surgically for carotid stenosis between 2004 and 2013. Histological analyses of carotid plaques were performed to assess the type of plaque (American Heart Association classification), the stability of the plaque, the extent of calcification, inflammation, and neovascularization, as well as the deposition of collagen and elastin. According to the scale of outcome measurement, logistic regression, ordinal regression, and multinomial regression analyses were applied. All results were adjusted for common risk factors of atherosclerosis.. Male sex was associated with more cellularity (odds ratio [OR], 1.56; P=0.003), more inflammatory infiltrates (OR, 1.75; P<0.001), and more neovascularization (OR, 1.47; P=0.010), but less calcification (OR, 0.78; P=0.090). Symptomatic patients were more likely to have a lower amount of elastin (OR, 0.71; P=0.057). Higher age was associated with increased calcification (OR, 1.23; P=0.009). Unstable plaques were found more frequently in symptomatic patients (OR, 1.60; 95% confidence interval, 1.14-2.25; P=0.007). A multinomial regression model revealed that age, sex, and history of neurological symptoms were significantly associated with specific plaque types (P=0.009, P<0.001, and P=0.017, respectively).. Plaque morphology differed between men and women and varied with age. Certain types of plaques (VI and VI/VII) as well as unstable plaques were significantly associated with a history of neurological symptoms. Thus, individual approaches (eg, in detection of plaque hemorrhage or thin fibrous caps) especially based on sex and age should be considered to identify patients at increased risk of stroke.

Topics: Age Factors; Aged; Aged, 80 and over; Carotid Stenosis; Cohort Studies; Collagen; Cross-Sectional Studies; Elastin; Endarterectomy, Carotid; Female; Humans; Inflammation; Logistic Models; Male; Middle Aged; Neovascularization, Pathologic; Plaque, Atherosclerotic; Sex Factors; Vascular Calcification

A correlation between the levels of antibodies to alpha-elastin (alpha-AEAb) and tropoelastin (tropo-AEAb) and the corresponding peptide concentration is found in human serum in health and disease. Serum elastin peptide and anti-elastin antibodies (AEAb) levels are age-related and vary with the stages of atherosclerotic vascular damage. This study aims to determine if elastin metabolism (assessed by the ratio of tropo-AEAb to alpha-AEAb) differs in patients with symptomatic carotid stenosis versus subjects with asymptomatic stenosis.. Alpha-AEAb and tropo-AEAb were measured by ELISA in blood sera of 65 patients with ultrasound verified high-grade symptomatic carotid stenosis (resulting in stroke 1-7 days before measurement) compared to 51 patients with asymptomatic stenosis.. Serum anti-alpha-elastin IgG levels are extremely increased in symptomatic versus asymptomatic carotid stenosis. The ratio of tropo-AEAb (reflecting elastin synthesis) to alpha-AEAb (a function of elastin degradation) was 3.7 in symptomatic stenosis versus 14.2 in asymptomatic stenosis (p<0.001).. There is a significant difference in elastin metabolism in patients with symptomatic carotid stenosis versus asymptomatic stenosis. The ratio of tropo-AEAb to alpha-AEAb as an index of elastin synthesis/degradation proves useful in investigation of atherosclerotic lesions and may represent a new immunologic marker for carotid plaque destabilization.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; Biomarkers; Carotid Stenosis; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Peptides

Topics: Antibodies; Carotid Stenosis; Elastin; Female; Humans; Male

Most acute cardiovascular events are caused by rupture of an atherosclerotic plaque. The incidence of cardiovascular events increases with age and inflammation is generally considered to be the main cause of increased plaque vulnerability. However, the relationship between age and plaque inflammation has not yet been fully clarified. The aim of our study was to determine if age-dependent plaque vulnerability is associated with increased plaque inflammation.. We collected 200 endarterectomy specimens, 103 of which were from patients 70 years or older. One-hundred and five patients had a recent cerebrovascular event, whereas the rest were asymptomatic despite significant carotid stenosis. Smooth muscle cell, lipid and macrophage content were analyzed by histology. Cytokines, growth factors and extracellular matrix proteins were analyzed in whole plaque homogenates by immunoassays and biochemical methods.. Plaques from elderly patients contained less IFN-γ, TNF-α, fractalkine, sCD40L, and elastin. Lipid and macrophage content was higher in plaques from symptomatic compared to asymptomatic patients in the elderly group, but not in younger patients. The elastin and collagen content was lower in plaques from symptomatic patients in both age groups. Plaques associated with symptoms also contained more TNF-α, IL-1β, IL-6, sCD40L, MIP-1β, MCP-1, RANTES and VEGF, regardless of age.. Our data imply that increased plaque vulnerability in the symptomatic elderly patients is associated with increased lipid accumulation and impaired tissue repair, rather than with increased plaque inflammation, compared to younger individuals.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Carotid Arteries; Carotid Stenosis; Collagen; Cytokines; Elastin; Endarterectomy, Carotid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Lipids; Macrophages; Male; Middle Aged; Plaque, Atherosclerotic

Strokes, a major cause of disability, are often caused by embolism from unstable carotid plaques. The aim of this study was to validate a biobank of human carotid endarterectomies as a platform for further exploration of pathways for plaque instability. For this purpose, we investigated the relationship between clinical parameters of plaque instability and expression of genes previously shown to be associated with either plaque instability or healing processes in the vessel wall.. A database of clinical information and gene-expression microarray data from 106 carotid endarterectomies were used.. Expression of matrix metalloproteinase (MMP)-9 and MMP-7 was 100-fold higher in plaques than in normal artery. In general, genes associated with inflammation (such as RANKL and CD68) were overexpressed in symptomatic compared with asymptomatic plaques. Plaques obtained from patients undergoing surgery within 2 weeks after an embolic event showed up-regulation of genes involved in healing reactions in the vessel wall (including elastin and collagen). Statin treatment, as well as echodense lesions, were associated with a more stable phenotype.. Here, we demonstrate that gene-expression profiles reflect clinical parameters. Our results suggest that microarray technology and clinical variables can be used for the future identification of central molecular pathways in plaque instability.

Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carotid Stenosis; Collagen; Databases, Genetic; Elastin; Endarterectomy, Carotid; Female; Gene Expression Profiling; Humans; Intracranial Embolism; Male; Matrix Metalloproteinase 7; Matrix Metalloproteinase 9; Middle Aged; Oligonucleotide Array Sequence Analysis; Phenotype; RANK Ligand; Statistics as Topic; Sweden; Up-Regulation; Wound Healing

During carotid endarterectomy (CEA), microemboli may occur, resulting in perioperative adverse cerebral events. The objective of the present study was to investigate the relation between atherosclerotic plaque characteristics and the occurrence of microemboli or adverse events during CEA.. Patients (n=200, 205 procedures) eligible for CEA were monitored by perioperative transcranial Doppler. The following phases were discriminated during CEA: dissection, shunting, release of the clamp, and wound closure. Each carotid plaque was stained for collagen, macrophages, smooth muscle cells, hematoxylin, and elastin. Semiquantitative analyses were performed on all stainings. Plaques were categorized into 3 groups based on overall appearance (fibrous, fibroatheromatous, or atheromatous).. Fibrous plaques were associated with the occurrence of more microemboli during clamp release and wound closure compared with atheromatous plaques (P=0.04 and P=0.02, respectively). Transient ischemic attacks and minor stroke occurred in 5 of 205 (2.4%) and 6 of 205 (2.9%) patients, respectively. Adverse cerebral outcome was significantly related to the number of microembolic events during dissection (P=0.003) but not during shunting, clamp release, or wound closure. More cerebrovascular adverse events occurred in patients with atheromatous plaques (7/69) compared with patients with fibrous or fibroatheromatous plaques (4/138) (P=0.04).. Intraoperatively, a higher number of microemboli were associated with the presence of a fibrous but not an atheromatous plaque. However, atheromatous plaques were more prevalent in patients with subsequent immediate adverse events. In addition, specifically the number of microemboli detected during the dissection phase were related to immediate adverse events.

Topics: Adult; Aged; Atherosclerosis; Carotid Arteries; Carotid Artery Thrombosis; Carotid Stenosis; Collagen; Elastin; Electroencephalography; Embolization, Therapeutic; Endarterectomy, Carotid; Female; Hematoxylin; Humans; Inflammation; Ischemia; Macrophages; Magnetic Resonance Imaging; Male; Microcirculation; Middle Aged; Muscle, Smooth; Phenotype; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Stroke; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Ultrasonography, Doppler, Transcranial; Wound Healing

Echolucent carotid plaques have been associated with increased risk for stroke. Histological studies suggested that echolucent plaques are hemorrhage- and lipid-rich, whereas echogenic plaques are characterized by fibrosis and calcification. This is the first study to relate echogenicity to plaque composition analyzed biochemically.. Echogenicity of human carotid plaques was analyzed by standardized high-definition ultrasound and classified into echolucent, with gray-scale median (GSM) <32 and echogenic with GSM > or =32. The biochemical composition of the plaques was assessed by fast-performance liquid chromotography and high-performance thin-layer chromotography.. As assessed biochemically (milligrams per gram [mg/g]), echolucent plaques contained less hydroxyapatite (43.8 [SD 41.2] mg/g versus 121.6 [SD 106.2] mg/g; P=0.018), more total elastin (1.7 [SD 0.4] mg/g versus 1.2 [SD 0.4] mg/g; P=0.008), and more intermediate-size elastin forms (1.2 [SD 0.3] mg/g versus 0.8 [SD 0.4] mg/g; P=0.018). There was no difference in collagen amount between echogenic and echolucent plaques, neither biochemically (15.3 [SD 3.7] mg/g versus 14.4 [SD 3.4] mg/g) nor histologically (13.4 [SD 4.9] % versus 13.0 [SD 5.6] %). Cholesterol esters, unesterified cholesterol, and triglycerides were increased in plaques associated with symptoms (22.5 [SD 23.3] mg/g versus 13.3 [SD 3.2]; P=0.04), but no differences were detected between echolucent and echogenic plaques (13.5 [SD 4.0] versus 20.2 [SD 21.5] mg/g). Similar results were obtained by Oil Red O staining (symptomatic 7.6 [SD 4.7] % versus asymptomatic 4.2 [SD 3.6] %; P=0.03; echolucent 5.9 [SD 4.1] % versus echogenic 5.0 [SD 4.0] % of area).. Echogenicity of carotid plaques is mainly determined by their elastin and calcium but not collagen or lipid content. In addition, echolucency is associated to higher elastin content.

Topics: Aged; Calcium; Carotid Stenosis; Chromatography, Liquid; Collagen; Elastin; Extracellular Matrix; Female; Humans; Lipids; Male; Ultrasonography

To measure serum concentrations of elastin-derived peptides (S-EDP) in patients with aneurysmal, occlusive and ulcerative manifestations of atherosclerotic disease.. S-EDP concentrations were measured by a competitive enzyme-linked immunosorbent assay in 10 patients with infrarenal aneurysms 5cm in diameter (AAA), 10 patients with distal aortic occlusive disease (AOD), 10 patients with symptomatic carotid stenosis (>or=70%) and plaque ulceration (SCS) and a control group of 10 patients with no similar specific manifestations of atherosclerotic disease (NAM).. S-EDP concentrations (median, range) were significantly higher in patients with AAA (42ng/ml, 35-52, p<0.001) and SCS (49ng/ml, 37-60, p<0.001) but not AOD (28ng/ml, 22-38, p=0.240) compared to NAM (26ng/ml, 19-36) patients.. Increased concentrations of S-EDP were associated with aneurysmal and ulcerative, but not occlusive, manifestations of atherosclerosis.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Aortic Aneurysm, Abdominal; Aortic Diseases; Arterial Occlusive Diseases; Arteriosclerosis; Carotid Stenosis; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Peptides; Pulmonary Disease, Chronic Obstructive; Smoking; Statistics, Nonparametric

Structure and content of atherosclerotic plaque varies between patients and may be indicative of their risk for embolisation. This study aimed to construct parametric images of B-scan texture and assess their potential for predicting plaque morphology. Sequential transverse in vitro scans of 10 carotid plaques, excised during endarterectomy, were compared with macrohistology maps of plaque content. Multidiscriminant analysis combined the output of 157 statistical and textural algorithms into five separate texture classes, displayed as ultrasound (US) texture classification images (UTCI). Visual comparison between corresponding UTCI and histology maps found the five texture classes matched with the location of fibrin, elastin, calcium, haemorrhage or lipid. However, histology preparation removes calcium and lipid and, so, can affect the structural integrity of atherosclerotic plaques. Soft tissue regions smaller than the UTCI kernel, (0.87 mm x 0.85 mm x 3.9 mm), such as blood clots, are also difficult to detect by UTCI. These factors demonstrate limitations in the use of histology as a "gold standard" for US tissue characterisation.

Topics: Arteriosclerosis; Calcium; Carotid Arteries; Carotid Stenosis; Elastin; Endarterectomy, Carotid; Fibrin; Hemorrhage; Humans; Image Processing, Computer-Assisted; In Vitro Techniques; Lipids; Ultrasonography

We designed an effective quadruple staining protocol that combines histochemistry (HC) and double-labeling immunohistochemistry (IHC: IHC) to stain simultaneously several different morphological features and cell types in vascular lesions. Morphometric image analysis to quantitate vascular wall thickening, lumen area, and proliferating smooth muscle cells on consecutive serial sections is adequate, but morphometric precision and dependable cellular characterization and co-localization could be obtained if analyses are performed on one tissue section. The development of a neointima in the rat carotid artery was induced by angioplasty with a balloon catheter. Tissues were stained for elastin by a modified van Gieson method, then processed for double-labeling IHC:IHC for proliferating cell nuclear antigen and smooth muscle actin followed by hematoxylin staining. The four resulting tissue stains labeled elastin filaments black, proliferating nuclei brown, smooth muscle actin red and nonproliferating nuclei blue. Our staining protocol improved the descriptive and quantitative analysis of relation between smooth muscle cell proliferation and protein expression. Also, neointimal thickening could be measured to analyze its relation to cellular proliferation. Providing one slide with four stains maximizes the information from a single slice of tissue, reduces slide preparation and analysis time, and overcomes the restriction of tissue sample availability. This technique can be applied to a wide spectrum of morphologic and morphometric studies.

Topics: Actins; Alkaline Phosphatase; Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Animals; Biomarkers; Carotid Arteries; Carotid Stenosis; Disease Models, Animal; Elastin; Endothelium, Vascular; Hematoxylin; Immunohistochemistry; Indicators and Reagents; Male; Muscle Fibers, Skeletal; Muscle, Smooth, Vascular; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Staining and Labeling

Formation of the atherosclerotic intima must involve altered metabolism of the elastin-rich arterial extracellular matrix. Proteases potentially involved in these processes remain unclear. This study examined the expression of the potent elastases cathepsins S and K in human atheroma. Normal arteries contained little or no cathepsin K or S. In contrast, macrophages in atheroma contained abundant immunoreactive cathepsins K and S. Intimal smooth muscle cells (SMC), especially cells appearing to traverse the internal elastic laminae, also contained these enzymes. Extracts of atheromatous tissues had approximately twofold greater elastase-specific activity than extracts of uninvolved arteries, mostly due to cysteine proteases. Cultured human SMC displayed no immunoreactive cathepsins K and S and exhibited little or no elastolytic activity when incubated with insoluble elastin. SMC stimulated with the atheroma-associated cytokines IL-1beta or IFN-gamma secreted active cathepsin S and degraded substantial insoluble elastin (15-20 microg/10(6) cells/24 h). A selective inhibitor of cathepsin S blocked > 80% of this elastolytic activity. The presence of cathepsins K and S at sites of vascular matrix remodeling and the ability of SMC and macrophages to use these enzymes to degrade elastin supports a role for elastolytic cathepsins in vessel wall remodeling and identifies novel therapeutic targets in regulating plaque stability.

Topics: Arteriosclerosis; Carotid Stenosis; Cathepsin K; Cathepsins; Cells, Cultured; Coronary Disease; Elastin; Enzyme Induction; Humans; Interferon-gamma; Muscle, Smooth, Vascular; RNA, Messenger; Tunica Intima