Mature Plaques Research Articles

The Microbiological Origin of Fluorescence Observed in Plaque on Dentures during QLF Analysis

The aim of this study was to determine the microbiological origin of plaque fluorescence observed during quantitative light-induced fluorescence (QLF) analysis. Plaque was sampled from dentures, because of easy accessibility and the homogeneous background provided by the denture tooth during imaging, and the acknowledged comparability to occlusal plaque. Forty removable poly(methyl methacrylate) dentures were screened for the presence of fluorescent plaque deposits during QLF analysis. Dentures were photographed, QLF images were recorded and samples of fluorescent plaque were taken. Plaque samples were cultured on fastidious anaerobe agar, Wilkins Chalgren agar and Sabourauds dextrose agar. Plates were screened under QLF and fluorescent colonies were subcultured and identified. Areas of red, orange and green fluorescence were detected on the fitting and non-fitting surfaces of dentures. The red and orange fluorescing species were Prevotella melaninogenica, Actinomyces israelii and Candida albicans, which are generally acknowledged to be secondary colonisers, present in more mature plaque. Green fluorescence was observed in streptococcal species (early colonisers) and Fusobacterium nucleatum (important organism in plaque development). Non-fluorescent colonies were also cultured. Plaque which accumulates on susceptible surfaces tends to be associated with caries, but it may be its maturity, rather than the presence of cariogenic streptococci, that is more likely to provide a microbiological link between red fluorescence and caries.

Genetics and molecular biology: macrophage ACAT depletion – mechanisms of atherogenesis

Genetics and molecular biology: macrophage ACAT depletion – mechanisms of atherogenesis

Targeting Amyloid-β Peptide (Aβ) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Aβ Precursor Protein (APP) Transgenic Mice

Passive immunization of murine models of Alzheimer disease amyloidosis reduces amyloid-beta peptide (Abeta) levels and improves cognitive function. To specifically address the role of Abeta oligomers in learning and memory, we generated a novel monoclonal antibody, NAB61, that preferentially recognizes a conformational epitope present in dimeric, small oligomeric, and higher order Abeta structures but not full-length amyloid-beta precursor protein or C-terminal amyloid-beta precursor protein fragments. NAB61 also recognized a subset of brain Abeta deposits, preferentially mature senile plaques, and amyloid angiopathy. Using NAB61 as immunotherapy, we showed that aged Tg2576 transgenic mice treated with NAB61 displayed significant improvements in spatial learning and memory relative to control mice. These data implicated Abeta oligomers as a pathologic substrate for cognitive decline in Alzheimer disease.

Amyloid in neurosurgical and neurological practice

The amyloidoses are a diverse group of diseases characterized by the deposition of specific proteins with distinct affinity to the dye Congo red, collectively called amyloid. The amyloidogenic proteins have acquired an abnormal, highly ordered, β-pleated sheet configuration with a propensity to self-aggregate. The amyloid may be distributed in different organs with a remarkable diversity. Two broad categories of amyloidoses are recognised: The systemic (consisting of the primary or light chain form, the secondary or reactive form and the familial or hereditary form) and the localised that target specific organs. A tropism of amyloid proteins to the neural tissue produces certain patterns of central nervous system diseases: cerebral amyloid angiopathy, a substrate of spontaneous intracerebral haemorrhage; mature neuritic plaques found in Alzheimer disease and a subset of prion diseases; a topographically restricted accumulation of extracellular proteins giving rise to tumour-mimicking masses, the amyloidomas; and finally, spinal extradural amyloid collections that occasionally are found in the context of rheumatoid arthritis. In this review article we present original illustrative cases of amyloid diseases of the central nervous system that may be encountered in neurosurgical and neurological practice. Molecular aspects and clinical management problems are discussed.

Peroxisome Proliferator-Activated Receptor-?? Agonists for Management and Prevention of Vascular Disease in Patients with and without Diabetes Mellitus

Inflammation is known to have a pathogenic role in atherosclerosis and the genesis of acute coronary syndromes. The peroxisome proliferator-activated receptor (PPAR)-gamma, which is expressed in many constituent cells of atheromatous plaques, inhibits the activation of several proinflammatory genes responsible for atheromatous plaque development and maturation. Agonists of this receptor, such as rosiglitazone and pioglitazone, are currently available for the treatment of type 2 diabetes mellitus, and several lines of evidence have shown that these drugs have antiatherogenic effects. Insulin resistance is associated with inflammation and has a key role in atherogenesis. The antiatherogenic and insulin sensitizing effects of the thiazolidinediones in patients with type 2 diabetes mellitus may be associated with this action. However, in recent years there has been growing evidence that the antiatherogenic effects of PPAR-gamma agonists are not confined to patients with diabetes mellitus. PPAR-gamma agonists have been shown to downregulate the expression of endothelial activation markers, reduce circulating platelet activity, improve flow-mediated dilatation and attenuate atheromatous plaque progression in patients without diabetes mellitus. These effects of PPAR-gamma agonists appear to result from both insulin sensitization and a direct modulation of transcriptional activity in the vessel wall. This review summarizes the current understanding of the role of PPAR-gamma agonists in atherogenesis and discusses their potential role in the treatment of coronary artery disease in patients with type 2 diabetes mellitus and in nondiabetic patients.

Matrix Metalloproteinases: A Potential Therapeutic Target in Atherosclerosis

Mature human atherosclerotic plaques are frequently characterized by a lipid-rich core covered by a fibrous cap composed of fibrillar collagens, elastin, proteoglycans and smooth muscle cells (SMC). Most sudden deaths due to acute myocardial infarction are caused by rupture of coronary atheroma, leading to a prothrombotic response followed by rapid occlusion of the artery. The accumulation of macrophage-derived foam cells in vulnerable shoulder regions of atherosclerotic plaques correlates with increased local release of matrix-degrading metalloproteinases (MMPs) and weak fibrous cap tissue. These findings suggest a potential role of macrophage-derived MMPs in the weakening and ultimate rupture of plaque structures. Consequently, several studies have focussed on the hypothesis that inhibiting MMP activity would reduce plaque volume and prevent plaque rupture and therefore would be useful in the treatment of atherosclerosis. However, current synthetic MMP inhibitors are not very specific and clinical results have so far been inconclusive. The development of selective inhibitors and focal gene transfer approaches may be better suited for the treatment of atherosclerosis.

The Proatherogenic Role of T Cells Requires Cell Division and Is Dependent on the Stage of the Disease

The mechanism by which T cells exert a proatherogenic potential is unclear. In order to determine whether this potential requires their replication, we crossed atherosclerosis-prone apolipoprotein E knockout mice (ApoE degrees) with transgenic mice in which exclusive and conditional ablation of dividing T cells relies on their specific expression of the herpes simplex type 1 thymidine kinase (TK) suicide gene. We first showed that conalbumin-immunized ApoE degrees TK mice mounted a significant immune response to the antigen that was fully and specifically blocked by an in vivo ganciclovir (GCV) treatment. Next, ApoE degrees TK mice and ApoE degrees mice were treated or not with GCV either during the first 4 weeks (GCV 1 to 4w), the last 4 weeks (GCV 5 to 8w), or during 8 weeks (GCV 1 to 8w). Strikingly, ApoE degrees TK mice displayed a dramatic decrease in lesion development in the GCV 1 to 8w and GCV 5 to 8w groups, whereas the GCV had no effect when administered during the first 4 weeks. In protected mice, the inflammatory parameters in lesions, the percentage of CD69+ CD3+ splenocytes, and the circulating natural killer T cells were reduced. The present study, therefore, shows that the proatherogenic potential of T cells is crucial in the progression of fatty streaks to mature plaques and requires cell division.

β-Amyloid secretion by human monocytes

In Alzheimer disease, plaque maturation is associated with an increase of activated microglia and neuroinflammation. Microglia are renewed by local proliferation and by recruitment from the circulating monocyte pool. The aim of the present study was to assess the secretion of amyloidogenic Aβ peptides by human monocytes in vitro. CD14 positive monocytes were isolated by magnetic activated cell sorting and grown in serum-free medium. Every 24h Aβ peptide secretion into the supernantant was quantified by Abeta-SDS-PAGE/Immunoblot. Cell differentiation was assessed by flow cytometry. Upon day 4 of culture in serum-free medium CD14+ monocytes had acquired a macrophage-like morphology. A strong increase in the expression of CD71 and CD40 indicated a maturation towards a macrophage-like phenotype. A time-dependent increase of Aβ peptide release was observed. The most prominent Aβ peptide was Aβ1–40 accounting for 45.5±1.0% of total Aβ. The second most abundant Aβ peptide was Aβ1–38like (23.8±2.0%), Aβ1–37 accounted for 12.0±0.6% of total Aβ. The highly amyloidogenic Aβ1–42 was not detectable. This Aβ release pattern of mononuclear phagocytes indicates that the APP metabolism differs quantitatively and qualitatively from that observed in plasma or CSF. The present findings indicate that monocytes are a potential source of Aβ peptides and that the Aβ release is increased upon differentiation into a macrophage-like phenotype.

Molecular mechanisms initiating amyloid beta-fibril formation in Alzheimer's disease.

The deposition of aggregated amyloid beta-protein (Abeta) in the human brain is a major lesion in Alzheimer' disease (AD). The process of Abeta fibril formation is associated with a cascade of neuropathogenic events that induces brain neurodegeneration leading to the cognitive and behavioral decline characteristic of AD. Although a detailed knowledge of Abeta assembly is crucial for the development of new therapeutic approaches, our understanding of the molecular mechanisms underlying the initiation of Abeta fibril formation remains very incomplete. The genetic defects responsible for familial AD influence fibrillogenesis. In a majority of familial cases determined by amyloid precursor protein (APP) and presenilin (PS) mutations, a significant overproduction of Abeta and an increase in the Abeta42/Abeta40 ratio are observed. Recently, it was shown that the two main alloforms of Abeta have distinct biological activity and behaviour at the earliest stage of assembly. In vitro studies demonstrated that Abeta42 monomers, but not Abeta40, form initial and minimal structures (pentamer/hexamer units called paranuclei) that can oligomerize to larger forms. It is now apparent that Abeta oligomers and protofibrils are more neurotoxic than mature Abeta fibrils or amyloid plaques. The neurotoxicity of the prefibrillar aggregates appears to result from their ability to impair fundamental cellular processes by interacting with the cellular membrane, causing oxidative stress and increasing free Ca(2+) that eventually lead to apoptotic cell death.

Variation in bacterial DGGE patterns from human saliva: over time, between individuals and in corresponding dental plaque microcosms

Eubacterial 16S rDNA fingerprints of human saliva and dental plaque microcosm biofilms grown in the multi-plaque artificial mouth (MAM) were characterised using denaturing gradient gel electrophoresis (DGGE). The stability of the bacterial community in the saliva of one individual collected over 7 years was assessed and compared with bacterial patterns in the saliva of 10 different individuals. DGGE was also used to assess changes in bacterial composition between saliva and mature plaque microcosms developed in the MAM from these 10 individual saliva samples. A relatively stable bacterial community (>87% concordance) was maintained within the individual oral environment of the standard donor over 7 years of monitoring. By comparison, DGGE fingerprint patterns of saliva from 10 different donors displayed greater variability (66% concordance). Variability between individual DGGE profiles increased further in mature plaque microcosms grown from the saliva of the 10 donors (52% concordance) with an increase in detected species diversity and evidence for conserved similarity and hence the maintenance of organisation during community development. These results suggest that stable ecological conditions were maintained long-term within the oral environment of the individual saliva donor but that transient fluctuations also occurred. The ecology and predominating microbiota in different individuals was host-specific and these differences were maintained to a degree during development into mature plaque microcosms. These findings also demonstrate the potential usefulness of applying DGGE to monitor temporal and developmental changes and possibly pathogenic patterns in oral bacterial communities from saliva and plaque.

C-reactive protein comes of age

Cardiovascular disease remains a leading cause of death throughout the world despite advances in its detection and treatment. Commonly used risk algorithms, such as the Framingham Risk Score fail to identify all affected individuals. Novel cardiovascular risk factors that identify these missed individuals would greatly improve overall care of patients. C-reactive protein (CRP), an inflammatory biomarker, has emerged as a leading candidate to fulfill this role. Based on the results of several prospective epidemiologic studies, CRP has emerged as one of the most powerful predictors of cardiovascular disease. This marker provides valuable information to clinicians in various clinical settings, ranging from overt cardiovascular disease, stable angina, presenting acute coronary syndromes and peripheral vascular disease, to the metabolic syndrome. Furthermore, CRP has been demonstrated to actively contribute to all stages of atherogenesis, participating in endothelial dysfunction, atherosclerotic-plaque formation, plaque maturation, plaque destabilization and eventual rupture. Thus, it might also serve as a therapeutic target. It is our contention that the future will see much wider use of CRP and CRP-driven therapies in clinical medicine, improving our ability to identify and manage cardiovascular disease.

Butyrylcholinesterase: impact on symptoms and progression of cognitive impairment

The most successful approach for treating people with Alzheimer’s disease to date has been by improving cholinergic transmission using cholinesterase inhibitors. Many of these drugs selectively inhibit acetylcholinesterase but some agents inhibit both acetylcholinesterase and butyrylcholinesterase. Recent evidence from studies examining butyrylcholinesterase in post mortem brain samples from dementia patients and examining the relationship between butyrylcholinesterase polymorphisms and the progression of cognitive impairment in dementia with Lewy bodies and Alzheimer’s disease add to a body of work suggesting that butyrylcholinesterase is present in key brain areas and may influence the maturation of plaques in Alzheimer’s disease. These accumulating data suggest that butyrylcholinesterase contributes to disease progression in people with dementia, which may be particularly important in individuals with more severe dementia as butyrylcholinesterase activity increases with disease development. It is a priority for future clinical trials to determine whether agents which inhibit butyrylcholinesterase and acetylcholinesterase have a greater clinical efficacy.

Determination of Elements in Native and Bypass Human Coronary Artery Plaque Deposits from the Same Heart Using Inductively Coupled Plasma-Mass Spectrometry

As part of an ongoing study on atherosclerotic arteries, the concentrations of 12 elements in a native and by-pass human coronary artery plaque deposits from five human hearts were determined using inductively coupled plasma-mass spectrometry (ICP-MS). These elements were Ca, P, Na, K, Mg, Zn, Cu, Pb, Fe, Al, Si, and S. For Zn, Ca, Pb, Fe, Al, and Si, the levels were at the fractional μmol/g levels and they probably played an unimportant role in plaque development. Sulfur levels varied from 23 to 140 µmols indicative of the possible presence of homocysteine, but there appeared to be no consistent relationship between by-pass and native concentrations. The calcium and phosphorus concentrations were relatively high in all cases, but the ratio of their molecular concentrations did not correspond to hydroxyapatite, which is conventionally considered to be the chemical form of calcium in heart plaque. In the mature native plaque, high calcium/phosphorus ratios indicated calcium in chemical forms other than hydroxyapatite. In undeveloped by-pass plaque, the phosphorus concentration was too high to be as hydroxyapatite but may be phospholipids. Because it is difficult to get suitable samples, only five heart samples were available. Therefore, these results should be treated as preliminary.

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity

Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.

Efficacy of plaque removal of the Sonicare Elite versus the Sonicare Advance from hard‐to‐reach sites

To compare the Sonicare Elite with the Sonicare Advance in terms of the reduction in supragingival plaque in the posterior, hard-to-reach areas of the mouth. This was a single-cohort, 6-week, two-treatment, single-blind, cross-over clinical trial that recruited 45 subjects. Plaque scores were recorded throughout the study using a modification of the Quigley and Hein plaque index (PI). All subjects had a minimum pre-brushing PI of 1.8 at screening following 24 h abstention from tooth cleaning. Subjects then used a Sonicare Advance powered toothbrush at home for 4 weeks for familiarisation purposes. At the next visit (2), subjects were given either the Sonicare Elite or the Sonicare Advance powered toothbrush for a further 2 weeks of home use. Twenty-four hours prior to visit 3, subjects abstained again from tooth cleaning. At visit 3, the PI was recorded pre- and post-tooth brushing and then all remaining "mature" plaque was removed professionally with a dental prophylaxis. After a further period of 24 h (to accumulate new plaque) without tooth brushing the subjects returned for visit 4 at which PIs were again recorded pre- and post-tooth brushing. The subjects were then given the second toothbrush in the cross-over sequence and attended for visits 5 and 6 at which the protocol for visits 3 and 4 was repeated. The Sonicare Elite powered toothbrush was more effective than the Sonicare Advance model in removing both mature and newly formed plaque. The magnitude of the differences between the toothbrushes for all posterior sites, interproximal and smooth surfaces, respectively, was 0.35 U (p<0.001), 0.39 U (p<0.001) and 0.32 U (p<0.001) of the modified Quigley and Hein PI. There was no evidence of a significant period effect comparing data from visits 5 and 6 against those from visits 3 and 4. There was, however, a significant visit effect with full-mouth (p<0.01), interproximal (p<0.001) and smooth surface (p<0.01) post-brushing plaque scores being significantly lower at visits 4 and 6 than at visits 3 and 5. The data support the observation that the Sonicare Elite toothbrush is more effective than the Sonicare Advance model in removing both newly formed and mature plaque from all posterior, interproximal and smooth tooth surfaces.

A nontransgenic mouse model shows inducible amyloid-beta (Abeta) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade.

The amyloid-beta (Abeta) peptide, a major pathological hallmark of Alzheimer's disease (AD), undergoes a cascade of interactions resulting in the formation of soluble aggregates and their conversion in the brain to insoluble deposits and mature senile plaques. Furthermore, the apoE4 isoform of apolipoprotein E (apoE), which is the major genetic risk factor of AD, is associated with increased Abeta deposition. It is not known how the different Abeta aggregates in the amyloid cascade are formed, contribute to the pathogenesis of AD, or are affected by apoE4. To investigate the initial aggregation stages underlying the amyloid cascade in vivo and how apoE affects them, we examined the effects of prolonged inhibition and subsequent reactivation of the Abeta-degrading protease neprilysin on deposition, disaggregation, and fibrillization of Abeta in apoE-transgenic and control mice. In control mice, intracerebroventricular infusion of thiorphan, which inhibits neprilysin, induced Abeta42 and Abeta40 deposition and fibrillization. On termination of thiorphan treatment, the number of Abeta deposits decreased, whereas the fibrillar Abeta deposits were unaffected. Similar treatments in apoE-deficient mice and mice transgenic for human apoE4 or apoE3 revealed that apoE4 enhances specifically the nucleation and aggregation of immunopositive Abeta deposits and that reversible disaggregation of these deposits and their irreversible conversion to fibrillar deposits are stimulated similarly by the different apoE isoforms. Deposition of Abeta and its enhancement by apoE4 were accompanied by increased astrogliosis both far from and near the Abeta deposits, suggesting that astrogliosis might be triggered by both insoluble and soluble Abeta aggregates.

Part of membrane-bound Aβ exists in rafts within senile plaques in Tg2576 mouse brain

To clarify whether rafts are the site of abnormal amyloid β protein (Aβ) deposition, we examined the ultrastructural localization of both flotillin-1 (pre-embedding) and Aβ (post-embedding) in Tg2576 mouse brains. After observing the exact areas of senile plaques by reflection contrast microscopy, we observed these same plaques under an electron microscope. Membrane-bound Aβ was predominantly observed on plasma membranes of small processes in diffuse plaques. Non-fibrillar and fibrillar Aβ was increased in primitive plaques, and the fibrillar form was predominant in mature plaques. The number of flotillin-1-positive rafts per field in mature plaques was prominently less than those outside of the plaques, in diffuse plaques and in primitive plaques. The colocalization of flotillin-1 with Aβ42 appeared approximately 10% of flotillin-1-positive rafts within senile plaques, while there was no colocalization found outside of the plaques. This study ultrastructurally demonstrated that part of membrane-bound Aβ exists in lipid rafts within senile plaques, and suggests that rafts could be one of the sites for initial Aβ deposition.

Cognitive correlates of Aβ deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes

Several transgenic mouse models of Alzheimer's disease (AD) have been developed that exhibit β-amyloid (Aβ) neuropathology and behavioural deficits. However, not all studies have investigated the relationship between the development of cognitive impairment and neuropathology. Therefore, temporal changes in cognition were investigated in male and female double-mutant APPswe×PS1.M146V (TASTPM) transgenic mice using an object recognition test and correlated with the development of cerebral Aβ neuropathology. Both male and female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and 10 months of age in the object recognition test, compared to wild-type littermates. There was no such cognitive impairment at 3 or 4 months of age. Quantitative immunohistochemistry using a battery of Aβ antibodies demonstrated that cerebral Aβ deposition was first apparent in 3-month-old mice, and it increased with age. The early appearance of cerebral Aβ deposits in the double-transgenic TASTPM mice supports the evidence that mutations in the PS1 gene accelerate Aβ deposition. The cerebral Aβ load was greater in female than in male TASTPM mice at all ages investigated. In the electron microscope, mature Aβ plaques comprising a fibrillar core surrounded by degenerating neurites and reactive glia were first observed in the cortex of TASTPM mice at 6 months of age, the same age at which cognitive impairment became apparent. These results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Aβ deposition, which first occurs 3 months earlier.

From conversion to aggregation: protofibril formation of the prion protein.

The ability to diagnose and treat prion diseases is limited by our current understanding of the conversion process of the protein from healthy to harmful isoform. Whereas the monomeric, benign species is well characterized, the misfolded conformations responsible for infectivity and neurodegeneration remain elusive. There is mounting evidence that fibrillization intermediates, or protofibrils, but not mature fibrils or plaques, are the pathogenic species in amyloid diseases. Here, we use molecular dynamics to simulate the conversion of the prion protein. Molecular dynamics simulation produces a scrapie prion protein-like conformation enriched in beta-structure that is in good agreement with available experimental data. The converted conformation was then used to model a protofibril by means of the docking of hydrophobic patches of the template structure to form hydrogen-bonded sheets spanning adjacent subunits. The resulting protofibril model provides a non-branching aggregate with a 3(1) axis of symmetry that is in good agreement with a wide variety of experimental data; importantly, it was derived from realistic simulation of the conversion process.

Dietary trans fatty acids and composition of human atheromatous plaques.

Dietary fatty acids are incorporated into atheromatous plaques mainly in the form of cholesterol esters. Physicochemical properties of the plaque (e. g. mechanical strength) depend on its fatty acid composition. Trans isomers of unsaturated fatty acids (TFA) are known to reduce the availability of fatty acid precursors for the synthesis of anticoagulant PG(1) and PG(3) prostaglandins. The present study was undertaken to determine the content of trans isomers in atheromatous plaques and to search for correlations between trans isomers in the plaque and adipose tissue. Atheromatous plaques were obtained from 31 patients who underwent surgery due to atherosclerotic stenosis of the abdominal aorta, iliac or femoral arteries. Fatty acids were extracted and separated as methyl esters using gas chromatography (GC) with an internal standard. Correlations were searched for with statistical methods, taking the level of significance as p < 0.05. We found spatial and positional isomers of sixteen- and eighteen-carbon fatty acids in plaques and adipose tissue, with elaidic acid (C18:1 trans-9) being the most abundant. Every plaque and adipose tissue sample contained linolelaidic acid (C18:2 trans-9 trans-12) which is derived exclusively from linoleic acid, as well as conjugated dienes of linoleic acid (CLA) produced during oxidative processes. The presence of trans isomers of fatty acids in the atheromatous plaque seems to be of relevance to plaque formation. Of much concern is the detection of elaidic and linolelaidic acids which adversely affect the physiologically important metabolism of eicosanoids. The TFA pool in adipose tissue has little effect on the amount of these acids in the atheromatous plaque. Apparently, the presence of TFA in atheromatous plaques is the result of processes taking place during plaque formation and maturation.