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To evaluate the causal relationship between genetically determined telomere length (TL) and atherosclerosis (AS). We performed a 2-sample Mendelian randomization (MR) study to assess the potential causal relationship between TL an...
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To evaluate the causal relationship between genetically determined telomere length (TL) and atherosclerosis (AS). We performed a 2-sample Mendelian randomization (MR) study to assess the potential causal relationship between TL and AS (coronary AS, cerebral AS, peripheral atherosclerosis (PAD), and AS, excluding cerebral, coronary, and PAD). The TL phenotype contained 472,174 participants, and the 4 subtypes of AS had 361,194, 218,792, 168,832, and 213,140 participants, all of European ancestries. The single nucleotide polymorphisms (SNPs) of TL strongly associated with the 4 atherosclerotic subtypes included in this study were 101, 92, 91, and 92, respectively. The odds ratios (ORs) and 95% confidence interval (CI) between TL and coronary AS calculated using inverse variance weighted (IVW) were 0.993 (0.988, 0.997), and the results were statistically significant ( P .05). “Egger-intercept test” showed that there was no horizontal pleiotropy ( P > .05); “leave-one-out analysis” sensitivity analysis showed that the results were stable and there were no instrumental variables with strong effects on the results; “MR- pleiotropy residual sum and outlier (PRESSO) test” showed 1 outlier for coronary AS and no outliers for the remaining subgroups. The results of the 2-sample MR analysis showed a causal association between TL and coronary AS but not with cerebral AS, PAD, and AS (excluding cerebral, coronary, and PAD). This may elucidate the observation that various vascular regions can be affected by AS but highlights the propensity of coronary arteries to be more susceptible to AS development.
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The first manifestation of atherosclerosis is commonly sudden death. Yet despite the fact that the disease has a long asymptomatic phase, diagnostic tests and treatments are largely only available to patients with symptoms. In thi...
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The first manifestation of atherosclerosis is commonly sudden death. Yet despite the fact that the disease has a long asymptomatic phase, diagnostic tests and treatments are largely only available to patients with symptoms. In this review, we discuss recent advances in technology and understanding of the disease process that are providing novel ways to identify patients at risk of having or developing asymptomatic atherosclerosis. We then review some of the disease-modifying drugs, such as antiplatelet agents, cholesterol-lowering drugs, and angiotensin-converting enzyme inhibitors, that can be used to reduce the risk of major adverse clinical events.
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In the past decades, peripheral arteries have represented a model for the comprehension of atherosclerosis as well as for the development of new diagnostic imaging modalities and therapeutic strategies. Peripheral arteries may rep...
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In the past decades, peripheral arteries have represented a model for the comprehension of atherosclerosis as well as for the development of new diagnostic imaging modalities and therapeutic strategies. Peripheral arteries may represent a window to study atherosclerosis. Pathology has prominently contributed to move the clinical and research attention from the arterial lumen stenosis and angiography to morphological and functional imaging techniques. Evidence from large and prospective cohort or randomized controlled studies is still modest. Nevertheless, several emerging imaging investigations represent a potential tool for a comprehensive "in vivo" evaluation of the entire natural history of peripheral atherosclerosis. This constitutes a demanding assignment, as it would be desirable to obtain both single-lesion focused and extensive arterial system views to achieve the most accurate prognostic information. Our narrative review rests upon the fundamental pathological evidence, summarizing the rapidly growing field of imaging of atherosclerosis in peripheral arteries and presenting a selection of both currently available and emerging imaging techniques.
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Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for resear...
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Spontaneous atherosclerosis is common in psittaciformes, and clinical signs associated with flow-limiting stenosis are encountered in pet birds. Nevertheless, a psittacine model of atherosclerosis has not been developed for research investigations. Sixteen captive-bred Quaker parrots (Myiopsitta monachus) were used in this study. While 4 control birds were fed a maintenance diet, 12 other birds were fed an atherogenic diet composed of 1% cholesterol controlling for a calorie-to-protein ratio for periods ranging from 2 to 8 months. The birds were euthanized at the end of their respective food trial period. Histopathology, transmission electron microscopy, and cholesterol measurement were performed on the ascending aorta and brachiocephalic and pulmonary arteries. Plasma lipoproteins, cholesterol, and triglycerides were also measured on a monthly basis. Significant atherosclerotic lesions were induced within 2 months and advanced atherosclerotic lesions within 4 to 6 months. The advanced lesions werehistologically similar to naturally occurring lesions identified in the same parrot species with a lipid core and a fibrous cap. Ultrastructurally, there were extracellular lipid, foam cell, and endothelial changes. Arterial cholesterol content increased linearly over time. Plasma cholesterol and low-density lipoprotein (LDL) significantly increased over time by an average of 5- and 15-fold, respectively, with a shift from high-density lipoprotein to LDL as the main plasma lipoprotein. Quaker parrots also exhibited high plasma cholesteryl ester transfer protein activity that increased, although not significantly, over time. This experiment demonstrates that in Quaker parrots fed 1% cholesterol, advanced atherosclerosis can be induced relatively quickly, and lesions resemble those found in other avian models and humans.
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Atherosclerosis and its clinical sequelae represent a huge and increasing global burden of morbidity and mortality in the form of coronary artery, peripheral vascular and cerebral vascular disease. The classical atherosclerotic le...
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Atherosclerosis and its clinical sequelae represent a huge and increasing global burden of morbidity and mortality in the form of coronary artery, peripheral vascular and cerebral vascular disease. The classical atherosclerotic lesion is an inflammatory fibrofatty plaque. Early notions of atherosclerosis were based on progressive calcification, however, atherosclerosis is now appreciated to be chronic and multifaceted, and the atherosclerotic plaque an "active biological environment." The interplay of endothelial dysfunction, lipid accumulation, immune response, vascular smooth muscle cell migration, matrix turnover, and calcification is gradually being unravelled. Such insights are already leading to changes in diagnosis and management of patients with atherosclerosis. Serum biomarkers, non-invasive imaging, and genetic testing are being actively investigated for future clinical application. In this review, we provide an overview of pathological findings and the current understanding of the pathogenesis of atherosclerosis and offer some insights into the direction of atherosclerosis research.
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In the beginning of this decade the Nobel laureate David Baltimore predicted that the 1990s would be the decade of the mouse, and the enormous bounty of biological information gained through the use of genetically modified mice ha...
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In the beginning of this decade the Nobel laureate David Baltimore predicted that the 1990s would be the decade of the mouse, and the enormous bounty of biological information gained through the use of genetically modified mice has turned his prediction into reality.
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Atherosclerotic vascular disease not only remains the leading cause of death in the Western countries, but it has become the most common cause of morbidity and mortality in the low- and middle-income countries as well. Therefore, ...
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Atherosclerotic vascular disease not only remains the leading cause of death in the Western countries, but it has become the most common cause of morbidity and mortality in the low- and middle-income countries as well. Therefore, better understanding of the pathogenesis of atherosclerotic disease and its prevention are of fundamental importance. It is well known that it affects sequentially the aorta followed by coronary, carotid, peripheral, and intracerebral arteries, with some individual variability. The mechanisms of progression are similar in each of the beds, with increasing lipid accumulation in the arterial wall along with macrophages and T-cell infiltration, paucity of smooth-muscle cell proliferation and collagen deposition, and endothelial-cell dysfunction and hypercoagulability playing an important role at the time of acute manifestations of the disease. Fundamental to this inflammatory process is the presence of classic risk factors, regardless of the involved territory. Therefore, the concept of palliative treatment must be reserved for only those who have progressed beyond preventive measures.
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Background and Purpose-The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warf...
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Background and Purpose-The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. This result has been attributed to the aggressive medical therapy used in SAMMPRIS, but an alternative hypothesis is that SAMMPRIS patients were at lower risk. We undertook analyses to evaluate these competing hypotheses.
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Integrins have been reported to mediate cell survival, proliferation, differentiation, and migration programs. For
this reason, the past few years have seen an increased interest in the implications of integrin receptors in ather...
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Integrins have been reported to mediate cell survival, proliferation, differentiation, and migration programs. For
this reason, the past few years have seen an increased interest in the implications of integrin receptors in atherosclerosis.
This review considers the potential role of integrins in atherosclerosis and also addresses why integrins present attractive
targets for drug design. It discusses the properties of the integrin-based chemotherapeutic agents currently under consideration
clinically and endeavours to provide insights into development of cardiovascular drugs using integrins as targets.
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