Plaque Structure Research Articles

Hochauflösende Bildgebung atherosklerotischer Gefäßwandläsionen der Karotiden durch die Magnetresonanztomografie

Stroke is the third most common cause of mortality in the United States with an incidence rate of approximately 700 000 deaths per year. As a means to prevent cerebrovascular events, current concepts advocate endarterectomy or carotid stenting in patients with advanced carotid disease. Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events and therefore both arterial stenosis and patient symptom status are taken as indications for interventional therapy. Several studies have shown that symptomatic subjects benefit more from a carotid endarterectomy than asymptomatic subjects: 3-6 carotid endarterectomies are needed to prevent one stroke per year in symptomatic subjects with > 70 % stenosis compared to 14 - 17 carotid endarterectomies in asymptomatic patients with > 50 % stenosis. It is commonly accepted today that factors other than the degree of luminal stenosis can determine a patient's symptom status, such as the composition or the superficial structure of atherosclerotic plaque. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading non-invasive imaging modality for atherosclerotic disease, especially within carotid arteries and other large vessels. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware and image acquisition protocols. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed.

The amniotic plaques in sheep of the Karagouniko breed

The structure of amniotic plaques and adjacent epithelium of full term ewes of the Karagouniko breed were studied using scanning electron microscopy (SEM) and light microcopy. The amniotic plaques appeared as cauliflower-like structures mainly trifurcate or as single papillae. The wall of their stems possessed numerous foldings and round openings. Of interest to note was the abundant vascularization observed in sections of the amniotic plaques. The adjacent amniotic epithelium to the plaques revealed a heterogenous surface which was composed of cells of various forms.

The desmosomal plaque and the cytoskeleton.

Two major plasma membrane domains are involved in the architectural organization of the cytoskeleton. Both are junctions of the adherens category characterized by the presence of dense plaques associated with the cytoplasmic surface of their membranes. The plaques serve as specific anchorage structures for two different types of cytoplasmic filaments. Intermediate-sized filaments (IF) of several types, i.e. cytokeratin IF in epithelial cells, desmin IF in cardiac myocytes and vimentin IF in arachnoidal cells of meninges, meningiomas and several other cells, attach to the desmosomal plaques, whereas actin-containing microfilaments associate with non-desmosomal adhering junctions such as the zonula adherens, fascia adherens and punctum adherens. The plaques of both kinds of adhering junctions contain a common acidic polypeptide of Mr 83,000 identical to 'band 5 protein' of bovine snout epidermal desmosomes. However, other plaque components are mutually exclusive to one of the two subclasses of adhering junctions. The desmosomal plaque structure, which does not contain vinculin and alpha-actinin, comprises representatives of cytoplasmic, non-membrane-integrated proteins such as desmoplakin(s) and the cytoplasmic portions of transmembrane glycoproteins such as 'band 3 glycoprotein'. The analysis of both categories of junction-associated plaques should provide a basis for understanding the establishment and the dynamics of junction-cytoskeleton interaction.

Photodynamic Therapy in Dentistry

Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemotherapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Applications of PDT in dentistry are growing rapidly: the treatment of oral cancer, bacterial and fungal infection therapies, and the photodynamic diagnosis (PDD) of the malignant transformation of oral lesions. PDT has shown potential in the treatment of oral leukoplakia, oral lichen planus, and head and neck cancer. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections. The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Disruption of plaque structure has important consequences for homeostasis within the biofilm. Studies are now leading toward selective photosensitizers, since killing the entire flora leaves patients open to opportunistic infections. Dentists deal with oral infections on a regular basis. The oral cavity is especially suitable for PACT, because it is relatively accessible to illumination.

Determination of atherosclerotic plaque temperature in large arteries

Atherosclerotic plaques with high probability of rupture can be characterized by the presence of a hot spot in the arterial wall, which forms due to accumulation of inflammatory cells in the plaque. This paper presents calculations of the arterial wall temperature distribution of arteries affected by plaque. This analysis characterizes the factors affecting plaque temperature, such as vessel geometry, plaque size, inflammatory cell density and distribution, and blood flow pattern. Three vessel types which present high occurrence of plaque are studied: a stenotic straight artery, an arterial bend and an arterial bifurcation corresponding to a human aorta, a coronary artery and a carotid bifurcation, respectively. The atherosclerotic plaque is located in the sites of low shear stress, and a local heat generation is introduced to account for the presence of inflamed plaque. It is shown that the plaque temperature correlates positively to inflammatory cell density and layer thickness, whereas the plaque temperature varies inversely with the depth of the inflammatory cell layer or fibrous cap. From the calculations, it is observed that the best spot to measure plaque temperature is between the middle and the far edge of the plaque where maximum temperature is located. The results contribute to understanding the physical characteristics of the plaque structure and its relationships to plaque temperature, and also suggest a tool to understand the arterial wall temperature measurements obtained with novel catheters.

Current Diagnostic Modalities for Vulnerable Plaque Detection

Rupture of vulnerable plaques is the main cause of acute coronary syndrome and myocardial infarction. Identification of vulnerable plaques is therefore essential to enable the development of treatment modalities to stabilize such plaques. Several diagnostic methods are currently tested to detect vulnerable plaques. Angiography has a low discriminatory power to identify the vulnerable plaque, but does provide information about the entire coronary tree and serves as guide for invasive imaging techniques and therapy. Angioscopy offers a direct visualization of the plaque surface and intra-luminal structures like thrombi and tears. However, angioscopy is difficult to perform, invasive and only the proximal part of the vessels can be investigated. IVUS (intravascular ultrasound) provides some insight into the composition of plaques. The detection of vulnerable plaques is mainly based on series of case reports with a lack of prospectivity and follow-up. Palpography, an IVUS derived technique, reveals information, which is not recognizable in IVUS. It can differentiate between deformable and non-deformable tissue, which enables the technique to detect vulnerable plaques with a positive predictive value. The clinical value of palpography is currently under investigation. Thermography assesses the temperature heterogeneity as an indicator of the metabolic state of the plaque. A coincidence of temperature rise and localization of vulnerable plaque was suggested. OCT (optical coherence tomography) can provide images with ultrahigh resolution utilizing the back-reflection of near-infrared light from optical interfaces in tissue. Drawbacks are the low penetration depth into tissue and the absorbance of light by blood. Raman spectroscopy can provide quantification about the molecular composition of the plaque. Long acquisition time, the low penetration depth and light absorbance by blood limit the performance of the technique. Another light emitting technique is NIR (near infrared spectroscopy), which identifies lipid loaded plaques and is tested currently in clinical trials. Non-invasive MRI (magnetic resonance imaging) and multislice spiral computed tomography (MSCT), with their excellent ability to identify lipid-rich tissue, have been utilized to characterize potentially vulnerable plaques foremost in non-moving structures like the carotid arteries. Due to the resolution of the techniques small plaque structure cannot be assessed. The role of non-invasive imaging in vulnerable plaque detection is currently under investigation. Several invasive and non-invasive techniques are currently under development to assess the vulnerable plaque. Most of the techniques show exiting features, but none have proven their value in an extensive in vivo validation and all have a lack of prospective data.

G Protein–Coupled Receptor G2A

See related article, pages 572–580 Atherosclerosis is, in large part, an inflammatory process. White blood cells of different lineages are essential components of the atherosclerotic plaque. More important than their numbers, white blood cells influence the structure of an atherosclerotic plaque, and the function of the vessel in which the plaque is present, by secreting a host of agents that affect resident vascular cells.1 Macrophages, derived from circulating monocytes, are one class of white blood cells that, as part of the atherosclerotic plaque, play a critical part in the progression of the plaque, and in compromising its structural integrity.1 Long before an atherosclerotic plaque is clinically detectable, one of the earliest steps in its genesis is the adhesion of circulating monocytes to the endothelium, and subsequent transmigration into the vessel wall. Because it is well-recognized that these very early stages are critical to plaque development, a great deal of energy has been devoted to trying to understand the mechanisms underpinning them. The work by Hedrick and colleagues in this issue of Circulation Research 2 adds to this understanding. This work examines the part of a G protein–coupled receptor, G2A, in modulating the interaction between monocytes and the vascular endothelium. Using mice that are deficient …

Calculation of arterial wall temperature in atherosclerotic arteries: effect of pulsatile flow, arterial geometry, and plaque structure

BackgroundThis paper presents calculations of the temperature distribution in an atherosclerotic plaque experiencing an inflammatory process; it analyzes the presence of hot spots in the plaque region and their relationship to blood flow, arterial geometry, and inflammatory cell distribution. Determination of the plaque temperature has become an important topic because plaques showing a temperature inhomogeneity have a higher likelihood of rupture. As a result, monitoring plaque temperature and knowing the factors affecting it can help in the prevention of sudden rupture.MethodsThe transient temperature profile in inflamed atherosclerotic plaques is calculated by solving an energy equation and the Navier-Stokes equations in 2D idealized arterial models of a bending artery and an arterial bifurcation. For obtaining the numerical solution, the commercial package COMSOL 3.2 was used. The calculations correspond to a parametric study where arterial type and size, as well as plaque geometry and composition, are varied. These calculations are used to analyze the contribution of different factors affecting arterial wall temperature measurements. The main factors considered are the metabolic heat production of inflammatory cells, atherosclerotic plaque length lp, inflammatory cell layer length lmp, and inflammatory cell layer thickness dmp.ResultsThe calculations indicate that the best location to perform the temperature measurement is at the back region of the plaque (0.5 ≤ l/lp ≤ 0.7). The location of the maximum temperature, or hot spot, at the plaque surface can move during the cardiac cycle depending on the arterial geometry and is a direct result of the blood flow pattern. For the bending artery, the hot spot moves 0.6 millimeters along the longitudinal direction; for the arterial bifurcation, the hot spot is concentrated at a single location due to the flow recirculation observed at both ends of the plaque. Focusing on the thermal history of different points selected at the plaque surface, it is seen that during the cardiac cycle the temperature at a point located at l/lp = 0.7 can change between 0.5 and 0.1 degrees Celsius for the bending artery, while no significant variation is observed in the arterial bifurcation. Calculations performed for different values of inflammatory cell layer thickness dmp indicate the same behavior reported experimentally; that corresponds to an increase in the maximum temperature observed, which for the bending artery ranges from 0.6 to 2.0 degrees Celsius, for dmp = 25 and 100 micrometers, respectively.ConclusionThe results indicate that direct temperature measurements should be taken (1) as close as possible to the plaque/lumen surface, as the calculations show a significant drop in temperature within 120 micrometers from the plaque surface; (2) in the presence of blood flow, temperature measurement should be performed in the downstream edge of the plaque, as it shows higher temperature independently of the arterial geometry; and (3) it is necessary to perform measurements at a sampling rate that is higher than the cardiac cycle; the measurement should be extended through several cardiac cycles, as variations of up to 0.7 degrees Celsius were observed at l/lp = 0.7 for the bending artery.

ZO-1 and ZO-2 Independently Determine Where Claudins Are Polymerized in Tight-Junction Strand Formation

A fundamental question in cell and developmental biology is how epithelial cells construct the diffusion barrier allowing them to separate different body compartments. Formation of tight junction (TJ) strands, which are crucial for this barrier, involves the polymerization of claudins, TJ adhesion molecules, in temporal and spatial manners. ZO-1 and ZO-2 are major PDZ-domain-containing TJ proteins and bind directly to claudins, yet their functional roles are poorly understood. We established cultured epithelial cells (1(ko)/2(kd)) in which the expression of ZO-1/ZO-2 was suppressed by homologous recombination and RNA interference, respectively. These cells were well polarized, except for a complete lack of TJs. When exogenously expressed in 1(ko)/2(kd) cells, ZO-1 and ZO-2 were recruited to junctional areas where claudins were polymerized, but truncated ZO-1 (NZO-1) containing only domains PDZ1-3 was not. When NZO-1 was forcibly recruited to lateral membranes and dimerized, claudins were dramatically polymerized. These findings indicate that ZO-1 and ZO-2 can independently determine whether and where claudins are polymerized.

MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis

The aims of this study were to compare a microsatellite polymorphism (PM) of matrix metalloproteinase (MMP)-9 in patients with carotid atherosclerosis and control population, and to assess the relationship between this PM and plaque structure. One hundred fifty patients referring to vascular diagnostic centers for suspected carotid atherosclerosis (at ultrasound examination: 110 positive, 40 negative) and controls (n=110) have been genotyped for MMP-9 PM. After controlling for risk factors, allelic and genotype frequencies were significantly different among the groups, with significant prevalence of long microsatellites in patients with carotid atherosclerosis. Long microsatellites (settled as 22 to 27 repeats) were associated with carotid atherosclerosis (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.9 to 9.2), compared with controls; an independent case control study on patients with coronary atherosclerosis confirmed such result. Binary logistic regression showed that hypertension, long microsatellites in MMP-9 PM and smoking habits were variables accounting for the difference between ultrasound-positive patients and controls. Long microsatellites were also associated to plaques with thin fibrous cap and echolucent core (OR, 13.1; 95% CI, 1.6 to 100). These alleles were slightly more represented in female patients (chi2 test=0.019; OR, 2.7; 95% CI, 1.2 to 6) but not associated with other risk factors. Plasma MMP-9 levels were related neither to MMP-9 PM nor to plaque type, and were related to gender and extension of atherosclerosis in carotid arteries. The number of repeats (> or =22 CA) in the microsatellite of MMP-9 promoter, but not MMP-9 plasma levels, is associated to carotid atherosclerosis and particularly to plaques with a thin fibrous cap.

Response to Letter by Moody et al

Response: We thank Dr Moody and colleagues for their comments on our article and agree that more streamlined protocols, extended coverage, and greater consistency in image quality are essential for plaque-imaging to be widely accepted in routine clinical practice. However, we strongly believe that efficiencies gained in scanning time should not be at the expense of a more comprehensive assessment of plaque structure and composition. Nearly 3 decades …

Maspin is physically associated with β1 integrin regulating cell adhesion in mammary epithelial cells

Maspin is a tumor-suppressor serpin (serine protease inhibitor), which inhibits cell invasion and migration. Here, we analyzed maspin function in cell adhesion in nontransformed mammary epithelial cells and investigated the underlying mechanism involved in this process. We report that maspin acts in the early steps in the cell adhesion process. Addition of recombinant maspin rapidly increased MCF-10A cell adhesion to the endogenously deposited matrix, and conversely both an antimaspin antibody (Ab) and maspin knockdown by RNA interference resulted in decreased cell adhesion. Mutation analyses revealed that a region of 86 amino acids located between aa 139 and aa 225 was responsible for maspin effect on adhesion. In addition, we show that maspin is associated with detergent-insoluble cortical cytoskeleton elements. Collectively, these results suggest that maspin is part of the supramolecular structure of the adhesion plaque and it modulates cell adhesion via a beta1 integrin-dependent mechanism.

Mechanical manipulation of Alzheimer’s amyloid β1–42 fibrils

The 39- to 42-residue-long amyloid β-peptide (Aβ-peptide) forms filamentous structures in the neuritic plaques found in the neuropil of Alzheimer’s disease patients. The assembly and deposition of Aβ-fibrils is one of the most important factors in the pathogenesis of this neurodegenerative disease. Although the structural analysis of amyloid fibrils is difficult, single-molecule methods may provide unique insights into their characteristics. In the present work, we explored the nanomechanical properties of amyloid fibrils formed from the full-length, most neurotoxic Aβ1–42 peptide, by manipulating individual fibrils with an atomic force microscope. We show that Aβ-subunit sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition. The fundamental unzipping force (∼23 pN) was significantly lower than that observed earlier for fibrils formed from the Aβ1–40 peptide (∼33 pN), suggesting that the presence of the two extra residues (Ile and Ala) at the peptide’s C-terminus result in a mechanical destabilization of the fibril. Deviations from the constant force transition may arise as a result of geometrical constraints within the fibril caused by its left-handed helical structure. The nanomechanical fingerprint of the Aβ1–42 is further influenced by the structural dynamics of intrafibrillar interactions.

Intravascular ultrasound image segmentation: a three-dimensional fast-marching method based on gray level distributions

Intravascular ultrasound (IVUS) is a catheter based medical imaging technique particularly useful for studying atherosclerotic disease. It produces cross-sectional images of blood vessels that provide quantitative assessment of the vascular wall, information about the nature of atherosclerotic lesions as well as plaque shape and size. Automatic processing of large IVUS data sets represents an important challenge due to ultrasound speckle, catheter artifacts or calcification shadows. A new three-dimensional (3-D) IVUS segmentation model, that is based on the fast-marching method and uses gray level probability density functions (PDFs) of the vessel wall structures, was developed. The gray level distribution of the whole IVUS pullback was modeled with a mixture of Rayleigh PDFs. With multiple interface fast-marching segmentation, the lumen, intima plus plaque structure, and media layers of the vessel wall were computed simultaneously. The PDF-based fast-marching was applied to 9 in vivo IVUS pullbacks of superficial femoral arteries and to a simulated IVUS pullback. Accurate results were obtained on simulated data with average point to point distances between detected vessel wall borders and ground truth <0.072 mm. On in vivo IVUS, a good overall performance was obtained with average distance between segmentation results and manually traced contours <0.16 mm. Moreover, the worst point to point variation between detected and manually traced contours stayed low with Hausdorff distances <0.40 mm, indicating a good performance in regions lacking information or containing artifacts. In conclusion, segmentation results demonstrated the potential of gray level PDF and fast-marching methods in 3-D IVUS image processing.

Isolation and characterization of bacteriophages infectingSalmonellaspp.

Bacteriophages infecting Salmonella spp. were isolated from sewage using soft agar overlays containing three Salmonella serovars and assessed with regard to their potential to control food-borne salmonellae. Two distinct phages, as defined by plaque morphology, structure and host range, were obtained from a single sample of screened sewage. Phage FGCSSa1 had the broadest host range infecting six of eight Salmonella isolates and neither of two Escherichia coli isolates. Under optimal growth conditions for S. Enteritidis PT160, phage infection resulted in a burst size of 139 PFU but was apparently inactive at a temperature typical of stored foods (5 degrees C), even at multiplicity of infection values in excess of 10 000. While neither isolate had characteristics that would make them candidates for biocontrol of Salmonella spp. in foods, phage FGCSSa1 behaved unusually when grown on two Salmonella serotypes at 37 degrees C in that the addition of phages appeared to retard growth of the host, presumably by the lysis of a fraction of the host cell population.

PARP‐1 inhibition, pharmacologically or genetically, reduces plaque size and promotes factors of plaque stability in an ApoE−/− mouse model of atherosclerosis

We have established a critical role for PARP-1 in cell death and the overall process of inflammation. Using an ApoE−/− mouse model of high fat diet (HF)-induced atherosclerosis, we report a positive correlation between apoptotic DNA damage within necrotic cores of atherosclerotic plaques and the activation of PARP-1 suggesting a role for this enzyme in the onset of disease. Administration of the potent PARP-1 inhibitor TIQ-A, twice a week, moderately reduced plaque size after 12 weeks of HF. Increasing TIQ-A injections to thrice a week significantly reduced plaque sizes. Plaques from TIQ-A treated mice contained thicker fibrous caps enriched with an abundance of smooth muscle cells (SMCs) and atrophic foam cells. Though lipid profile in sera and overall collagen synthesis in aortas were not different, marked reduction in macrophage recruitment, increase in SMC transmigration into the intimal space with concomitant increase in collagen content in plaques of TIQ-A treated mice was observed. Such traits are cardinal for atherosclerotic plaque integrity. These results were corroborated by the similar effect PARP-1 heterozygocity exerted on plaque size and structure in ApoE−/− mice. Using an in vitro model of vascular inflammation, we found that PARP-1 inhibition, by TIQ-A or gene knockout, conferred significant protection to ex vivo-generated foam cells and SMC after H2O2 treatment. Our results suggest that PARP-1 inhibition not only reduces plaque size, but may have an important role in plaque structure and stability through its modulation of cell death Support: NIH-1P20RR18766 and HL072889 to H. B.

Differentiation role of PARP‐1 in p65 NF‐kB translocation into nuclei of primary aortic smooth muscle cells in response to TNF, LPS or H2O2: Implication in atherosclerosis

Using a mouse model of high fat diet (HF)-induced atherosclerosis, we report a correlation between DNA damage within atherosclerotic plaques, expression of NF-kB-dependent inflammatory factors and the activation of PARP-1 suggesting a role for PARP-1 in the onset of the disease. Administration of the PARP-1 inhibitor TIQ-A caused a reduction in size and changes in structure of atherosclerotic plaques after 12 weeks of HF diet. Plaques from TIQ-treated mice contained thicker fibrous caps with a high number of smooth muscle cells (SMCs) and atrophic foam cells with minimal macrophage recruitment. Using an in vitro cell culture model of vascular inflammation and fluorescently tagged p65 NF-kB, we show that the translocation of this transcription factor into nuclei of primary aortic SMC required PARP-1 expression in response to LPS or H2O2 but not in response to TNF. Similarly, degradation of I-kB alpha was defective in LPS or H2O2-treated but not in TNF-treated PARP-1−/− SMC. However, the TNF-triggered p65 NFkB translocation and I-kB alpha degradation did not induce expression of the NF-kB-dependent iNOS in PARP-1−/− SMC. These results demonstrate that p65 NF-kB translocation to nuclei and the concomitant degradation of I-kB alpha are not sufficient for expression of inflammatory factors but required expression of PARP-1. These results suggest a role for PARP-1 in the onset of atherosclerosis through a mediation of the signal transduction of NF-kB and the concomitant expression of inflammatory factors. Support: NIH-1P20RR18766 and HL072889 to H. B.

A secondary disruption of the dmpA gene encoding a large membrane protein allows aggregation defective Dictyostelium rasC− cells to form multicellular structures

The disruption of the gene encoding the Dictyostelium Ras subfamily protein, RasC, results in a strain that does not aggregate and has defects in both cAMP signal relay and cAMP chemotaxis. Disruption of a second gene in the rasC − strain by Restriction Enzyme Mediated Integration produced cells that were capable of forming multicellular structures in plaques on bacterial lawns. The disrupted gene ( dmpA) encoded a novel membrane protein that was designated Dmp1. Although the rasC −/ dmpA − cells progressed through early development, they did not form aggregation streams on a plastic surface under submerged starvation conditions. Phosphorylation of PKB in response to cAMP, which is significantly reduced in rasC − cells, remained low in the rasC −/ dmpA − cells. However, in spite of this low PKB phosphorylation, the rasC − / dmpA − cells underwent efficient chemotaxis to cAMP in a spatial gradient. Cyclic AMP accumulation, which was greatly reduced in the rasC − cells, was restored in the rasC −/ dmpA − strain, but cAMP relay in these cells was not apparent. These data indicate that although the rasC −/ dmpA − cells were capable of associating to form multicellular structures, normal aggregative cell signaling was clearly not restored. Disruption of the dmpA gene in a wild-type background resulted in cells that exhibited a slight defect in aggregation and a more substantial defect in late development. These results indicate that, in addition to the role played by Dmp1 in aggregation, it is also involved in late development.

Update on Coronary Angioscopy: Review of a 20‐Year Experience and Potential Application for Detection of Vulnerable Plaque

Predicting the occurrence of future acute coronary syndromes remains an important challenge of contemporary cardiology. It is thought that detecting the individual vulnerable plaques in patients can be an important step to preventing myocardial infarction and sudden cardiac death. Coronary angioscopy can provide detailed information of the luminal surface of plaque, such as color, thrombus, or disruption, and is one of a few possibly useful imaging modalities for identifying vulnerable plaques. During its 20-year history, coronary angioscopy has been used as a diagnostic tool or to guide coronary angioplasty, and has contributed to our understanding of the pathophysiology of coronary artery disease. Yellow plaques seen during angioscopy seem to have many characteristics of high risk or vulnerable plaques, most consistent with the thin-cap fibroatheroma. Moreover, differences in yellow color have been reported to reflect differences in the structure or composition of plaques. Development of quantitative methods to assess plaque color and histopathologic correlations in conjunction with prospective natural history studies may lead to advances in vulnerable plaque detection by coronary angioscopy. Although current angioscopic devices are limited by the need to displace the column of blood in order to see the vessel wall, and by the lack of quantitative colorimetric methods, advances in technology may lead to new device versions that could be practical for expanded clinical use.

Plaques of Alzheimer’s disease originate from cysts of Borrelia burgdorferi, the Lyme disease spirochete

Here is hypothesized a truly revolutionary notion that rounded cystic forms of Borrelia burgdorferi are the root cause of the rounded structures called plaques in the Alzheimer brain. Rounded "plaques' in high density in brain tissue are emblematic of Alzheimer's disease (AD). Plaques may be conceptualized as rounded "pock mark-like" areas of brain tissue injury. In this century, in brain tissue of AD, plaques are Amyloid Plaques according to the most up to date textbooks. In the last century, however, Dr. Alois Alzheimer did not require amyloid as the pathogenesis for either the disease or for the origin of its plaques. Surely, amyloid is an event in AD, but it may not be the primal cause of AD. Indeed in plaques, amyloid is regularly represented by the "congophilic core" structure which is so named because the waxy amyloid material binds the congo red stain and is congophilic. However an accepted subset of plaques in AD is devoid of a congophilic amyloid core region (these plaques "cotton wool" type plaques, lack a central congophilic core structure). Furthermore, there is "plaque diversity" in Alzheimer's; small, medium and large plaques parallel variable cystic diameters for Borrelia burgdorferi. Perturbations of AD plaque structure (i.e. young plaques devoid of a central core and older plaques with or without a central core structure) offer room for an alternate pathway for explanation of ontogeny of the plaque structures. If amyloid is not required to initiate all of the possible plaques in Alzheimer's, is it possible that amyloid just a by product of a more fundamental primal path to dementia? If a byproduct status is assigned to amyloid in the realm of plaque formation, then is amyloid also an epiphenomenon rather than a primary pathogenesis for Alzheimer's disease. In the "anatomy is destiny" model, cysts of borrelia are always round. Why then not accept roundness as a fundamental "structure determines function" argument for the answer to the mystery of why Alzheimer plaques are always round? Parataxis causality, a concept borrowed from philosophy, is the error that comes from linking two events, which occur contemporaneously or in close proximity to one another with a cause and effect relationship. Parataxis tells us that what appears to be cause and effect in the couplet "amyloid plaque" merely by a proximity relationship may be "spurious causality" which is a cognitive dead end.