Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is regarded as a chronic disease that begins in early life. While the main underlying mechanism of atherosclerosis is nowadays unequivocally attributed to a low-grade inflammatory reaction, the spectrum of aetiological conditions is far from being fully elucidated. Both viruses and bacteria have been suggested to intervene at various stages of atherosclerosis development, although a clear pathogenic link between infection and atherosclerosis remains debatable. As one key event in atherogenesis involves a perturbation of the protective mechanisms normally posed by the arterial endothelium, a number of studies have enquired into the possible detrimental effects of microbes and their components on the endothelial cells. This review aims to scrutinize the current literature in this regard, and to suggest several possible directions for future studies.
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PMID:Arterial endothelial injury due to infection in childhood: ticking bomb or innocent bystander? 1570 71

Atherosclerosis is a chronic disease potentially involving the whole arterial system that causes a spectrum of clinical manifestations ranging from acute myocardial infarction to stable angina or stroke. The continuous accumulation of lipids, and fibrous and inflammatory elements in the arterial wall of the coronary tree leads to progressive lumen narrowing with subsequent ischemia and symptom-limited exercise. Acute coronary syndromes (unstable angina, acute myocardial infarction) have a more complex and dynamic pathogenesis of which coronary plaque rupture and thrombosis represent only the final common pathway that suddenly compromises resting coronary flow. As only some plaques lead to clinical manifestations whereas many others remain asymptomatic, the aim of this review was to analyze the complex mechanisms leading to plaque complication and rupture with respect to systemic and local features.
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PMID:[Pathogenesis of acute coronary syndromes: the activated plaque]. 1594 13

Atherosclerosis is a chronic disease of the vasculature that is influenced by multiple factors that involve a complex interplay between some components of the blood and the arterial wall. Inflammation and oxidative stress have key roles in atherogenesis. The production of F2-isoprostanes (F2-IPs), thromboxane A2 (TxA2) and prostacyclin (PGI2) increases in atherosclerosis, and recent studies show that pharmacological modulation of their biosynthesis and biological activities are important therapeutic targets for managing atherosclerosis. In this review, we highlight recent breakthroughs in the roles of F2-IPs, TxA2 and PGI2 in atherogenesis, and identify pertinent therapeutic targets.
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PMID:Thromboxane, prostacyclin and isoprostanes: therapeutic targets in atherogenesis. 1624 3

Chronic diseases such as atherosclerosis, arthritis, diabetes, and cancer are among major public health concerns. To understand their cumulative risk factors and antecedents, a chronic disease databank consisting of time-oriented, multidisciplinary longitudinal data, prospectively collected on consecutive patients and describing their clinical courses, provides a systematic anthology of patient reported outcome (PRO) data. ARAMIS, which began in the mid-1970s, was the first large-scale chronic disease data bank system. Outcomes data are collected using the Health Assessment Questionnaire (HAQ), a well established PRO instrument that collects patient-centered data in the areas of disability, pain and other symptoms, adverse effects of treatment, economic impact, and mortality. More than 900 peer-reviewed studies have emanated from ARAMIS since its inception. In the earlier days, and even today, ARAMIS had to invent its own tools for the study of these new sciences. ARAMIS has made dominant contributions to the understanding of PROs and to helping improve treatment and health outcomes in rheumatoid arthritis (RA), osteoarthritis (OA), scleroderma, lupus, aging, and drug side effects. It continues to traverse terrain with participation in the NIH "Roadmap" project, the Patient Reported Outcome Measurement Information System (PROMIS). PROMIS is designed to provide improved assessment of health status across all chronic illnesses as part of an improved infrastructure for clinical research. As initiator of the rich history of chronic disease data banks with "rolling" consecutive open patient cohorts, ARAMIS has enabled the study of real-world PROs in rheumatology, with a wealth of resultant improved approaches to treatment, outcome, cost effectiveness, and quality of life.
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PMID:The Arthritis, Rheumatism and Aging Medical Information System (ARAMIS): still young at 30 years. 1627 1

Atherosclerosis is a chronic disease with high morbidity and mortality around the globe. It is characterized by chronic inflammation of the vessel wall, which is perpetuated by the continuous migration of cells to and within the atherosclerotic lesion. Chemokines (CK) and chemokine receptors (CKR) together with other chemoattractants and adhesion molecules are major mediators facilitating this process. Many CK/CKR (CC, CX3C and CXC) and other chemoattractants (e.g. leukotrienes) have been implicated in atherogenesis, but only a few have been validated as pathogenic by in vitro assays, in vivo experiments using gene-targeted animal models and genetic studies. Promising attempts are currently made to inhibit CK-dependent cell recruitment to lesion by using neutralizing antibodies, mutant proteins, viral and synthetic inhibitors or receptor antagonists. Some of the therapeutics have already entered clinical trials for other conditions and are about to be tested in human atherosclerosis. However, our limited understanding of the complex CK system and the functional specialization of individual CK/CKR, translatability of animal research into human population, limitations of current imaging techniques and surrogate markers for evaluation of the benefits of potential anti-CK compounds are still hampering therapeutic exploitation of the CK system in atherosclerosis. Hopefully we will be able to solve many of these issues in the near future and use this approach to control atherosclerotic disease in man.
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PMID:Chemokines as potential therapeutic targets in atherosclerosis. 1645 97

Clinical and epidemiologic studies have suggested an association between infectious agents and chronic inflammatory disorders and cancer. Better understanding of microbial pattern-recognition receptors and innate immune signaling pathways of the host is helping to elucidate the connection between microbial infection and chronic disease. We propose that a key aspect of pathogenesis is an aberrant epithelial barrier that can be instigated by microbial toxins, environmental insults, or the genetic predisposition of the host. Loss of epithelial integrity results in activation of resident inflammatory cells by microbial invaders or endogenous ligands. When coupled with a failure of normal control mechanisms that limit leukocyte activation, a cascade is established that induces chronic inflammation and its consequences. Here, we outline this mechanistic framework and briefly review how alteration of innate immune response genes in murine models can provide insights into the potential microbial origins of diverse conditions including Crohn's disease, psoriasis, atherosclerosis, diabetes, and liver cancer.
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PMID:Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. 1649 91

Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and weaken the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways, in which the two anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta play a critical role. The purpose of this review is to bring together the current information concerning the role of cytokines in the development, progression, and complications of atherosclerosis. Specific emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to pathogenic (innate and adaptive) and regulatory immunity in the context of atherosclerosis. Based on our current knowledge of the role of cytokines in atherosclerosis, we propose some novel therapeutic strategies to combat this disease. In addition, we discuss the potential of circulating cytokine levels as biomarkers of coronary artery disease.
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PMID:Cytokines in atherosclerosis: pathogenic and regulatory pathways. 1660 Dec 68

Atherosclerosis is a chronic disease of the arteries whose development involves a local inflammatory response characterized by the activation of different cells such as macrophages, T-lymphocytes, smooth muscle cells (SMCs) and endothelial cells (ECs). This review will summarize recent evidence for a modulatory role of the nuclear receptor ROR-alpha in cardiovascular disease.
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PMID:Potential roles of ROR-alpha in cardiovascular endocrinology. 1660 83

T cells are involved in the pathogenesis of atherosclerosis. We aimed to search for any association between the peripheral T-cell activities and atherogenic risk factors in healthy subjects. Fifty male volunteers (age 22.0 +/- 2.4 years) were enrolled. No subject had any chronic disease or was under any drug treatment. Lymphocytes were isolated from heparinized venous blood and the proliferative responses to phytohemagglutinin (PHA) were measured from the amount of radioactive thymidine uptake by the lymphocyte DNA. T-cell activity responses of patients with a family history of coronary events were compared with others. The activity responses of smokers were compared with nonsmokers. Subjects with a positive family history of coronary events had higher PHA stimulated T-cell response and delta cpm (P < 0.05 for each). Total and low-density lipoprotein cholesterol levels of the subjects with a positive family history of cardiovascular events were positively correlated with the PHA-activated T-cell responses (P = 0.022, r = 0.604 and P = 0.015, r = 0.635, respectively). There was no significant difference between the T-cell activity responses of smokers and nonsmokers. No correlation was found between the biochemical parameters and T-cell activities in these groups. Peripheral T-cell activity responses to PHA are higher in the asymptomatic relatives of patients with coronary events. This may be a clue for the familial tendency of atherosclerotic diseases. Further follow-up studies are necessary to investigate the relationship.
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PMID:Asymptomatic kindred of patients with coronary events have increased peripheral T-cell activities. 1686

The "number-needed-to-treat" (NNT) was introduced about 15 years ago and has gained widespread use. It has been claimed to be "easy to understand" and gives "intuitive meaning". When used to measure the effectiveness of interventions targeting chronic disease processes e.g. atherosclerosis and osteoporosis, NNT (as well as relative and absolute risk reduction) does not capture the crucial time component, a fact that has important consequences: NNT varies over time, it may not mean that adverse events (fractures, myocardial infarctions etc.) are avoided, but simply that they are postponed. Finally, empirical studies indicate that lay people and doctors misunderstand NNT. We recommend that NNT be used with considerable care. There is probably no single effect measure that is able to convey all necessary information.
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PMID:Number-needed-to-treat (NNT)--needs treatment with care. 1686 64


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