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

The so-called classic risk factors of coronary heart disease (CHD) do not explain all its clinical and epidemiological features. Recent evidence suggests that certain infections, among them dental infections, are involved in the pathogenesis of CHD. Case-control studies have revealed an association between dental infections and acute myocardial infarction and chronic coronary heart disease. A large epidemiological survey revealed an association between missing teeth and CHD and a recent 14-year follow-up of 9760 individuals showed that periodontitis is associated with an increased risk of coronary heart disease. Preliminary results suggest that the severity of dental infections correlates with the extent of coronary atheromatosis. Individuals with severe dental infections also have higher level of von Willebrand factor antigen, leukocytes and fibrinogen. Streptococcus sanguis has been shown to aggregate human platelets in vitro. The mechanism behind the association between dental infections and CHD could be the effect of bacteria on the cells taking part in the pathogenesis of atherosclerosis and arterial thrombosis.
 ...
PMID:Dental infections as a risk factor for acute myocardial infarction. 813 88

Matrix metalloproteinases (MMPs), also called matrixins, function in the turnover of extracellular matrix components. These enzymes are considered to play important roles in embryo development, morphogenesis and tissue remodeling, and in diseases such as arthritis, periodontitis, glomerulonephritis, atherosclerosis, tissue ulceration, and in cancer cell invasion and metastasis. All MMPs are synthesized as preproenzymes and most of them are secreted from the cells as proenzymes. Thus, the activation of these proenzymes is one of the critical steps that leads to extracellular matrix breakdown. This review describes recent progress made to elucidate the activation mechanisms of pro-matrixins which include extracellular stepwise activation common to most proMMPs, cell surface activation of progelatinase A and procollagenase 3, and intracellular activation of prostromelysin 3 and pro-membrane-type-1 MMP.
 ...
PMID:Activation mechanisms of matrix metalloproteinases. 916 65

This paper evaluates the current information on the relationship between oral disease (specifically periodontitis) and atherosclerosis/coronary heart disease (CHD) to determine whether the information is sufficient to conclude that periodontitis is a risk factor for atherosclerosis/CHD. As background for this evaluation, the term "risk factor" is defined, and the 3 criteria used to establish exposures as risk factors are reviewed. In addition, epidemiologic criteria for defining an exposure as causal are presented. The available evidence then is evaluated according to the criteria for causality, which are extensions of the criteria for establishing a risk factor. This review is done in the context of the relationship between atherosclerosis/CHD and inflammation. A number of findings are briefly reviewed that link inflammation and atherosclerosis/CHD, such as: 1) prior flu-like symptoms were more common in cases of myocardial infarction than in concurrently sampled controls; 2) high levels of cytomegalovirus antibody titers were associated with elevated carotid intimal-medial wall thickness 18 years later; 3) prior infection with cytomegalovirus was a strong independent risk factor for restenosis after coronary atherectomy; 4) dental infections were more common in cases of cerebral infarction compared to community controls matched on age and sex; and 5) the gingival index was significantly correlated with fibrinogen and white cell counts in periodontal patients and controls, adjusted for age, smoking, and socioeconomic status. Three case-control studies and 5 longitudinal studies investigating the relationship between dental conditions and atherosclerosis/CHD are reviewed in terms of strength of associations, consistency of associations, specificity. of associations, time sequence between exposure and outcome, and degree of exposure and outcome. Related to the last criterion, new findings are presented which indicate that the extent of the periodontal infection, a measure reflecting microbial burden, also is related to onset of new CHD events. Our previously published model describing the potential biological mechanisms underlying the associations found is reviewed. This model places the associations into a context of an intrinsic or acquired hyperinflammatory monocyte trait that results in a more intense inflammatory response to lipopolysaccharide (LPS) challenges, such as periodontal infections. This hyperinflammatory response may promote atheroma formation and thromboembolic events. finally, new findings from ongoing animal studies are presented, indicating that high fat diets in atherosclerotic-susceptible mice induce greater inflammatory responses to Porphyromonas gingivalis challenges. We conclude that the available evidence does allow an interpretation of periodontitis being a risk factor for atherosclerosis/CHD. This conclusion, however. is made with some qualifications. While the associations found across a wide variety of subjects are remarkably consistent, for the most part they are represented by incidence odds ratios around 2.0. While this level of association would result in oral conditions contributing to a large number of CHD cases, it is possible that associations of this magnitude are due to bias in the study designs. In addition, some studies report that periodontitis is associated with all-cause mortality and low birth weight infants. These multiple associations detract from the credibility of periodontitis as a risk factor, as specificity of association is more often related to causality. However, all-cause mortality may largely be driven by mortality from cardiovascular events: and some exposures, such as smoking. are indeed risk factors for multiple conditions. On the other hand, current findings regarding the associations between oral conditions and atherosclerosis/CHD imply that the criteria for causality may be met in the not-too-distant future.
 ...
PMID:Periodontitis: a risk factor for coronary heart disease? 972 97

Periodontitis and atherosclerosis have complex etiologies, genetic and gender predispositions, and potentially share many risk factors-the most significant of which may be smoking status. These diseases also have many pathogenic mechanisms in common. It is becoming increasingly clear that infections and chronic inflammatory conditions such as periodontitis may influence the atherosclerotic process. The severity and chronicity of periodontal disease provides a rich source of subgingival microbial and host response products and effects over a long time period. The objective of this review is to consider the mechanisms whereby diseases such as periodontitis, which is chronic and Inflammatory In nature and initiated by microbial plaque, can predispose to atherosclerosis. In common with periodontal disease. the pathogenesis of atherosclerosis is not completely understood and both diseases are currently under Intensive investigation. Two main processes in particular are worthy of consideration and may provide the link between these 2 diseases, namely the lipopolysaccharide-related responses and the hyperresponsive monocyte phenomenon. Insufficient experimental evidence exists, however, to further support these hypotheses at present and clearly more research is needed on both of these processes and the interrelationships between both diseases.
 ...
PMID:Periodontal diseases' contributions to cardiovascular disease: an overview of potential mechanisms. 972 98

Cardiovascular diseases, including atherosclerosis and myocardial ischemia, occur as a result of a complex set of genetic and environmental factors. During periodontitis, dental plaque microorganisms may disseminate through the blood to infect the vascular endothelium and contribute to the occurrence of atherosclerosis and risk of myocardial ischemia and infarction. Myocardial ischemia and infarction are often preceded by acute thromboembolic events. In an in vitro model of thrombosis, certain dental plaque bacteria induce platelets to aggregate. Aggregation of platelets is induced by the platelet aggregation-associated protein [PAAPJ expressed on plaque bacteria, including Streptococcus sanguis and Porphyromonas gingivalis. Intravenous infusion of S. sanguis into rabbits has been shown previously to cause changes in the electrocardiogram (ECG), heart rate, blood pressure, and cardiac contractility. These changes are consistent with the occurrence of myocardial infarction. The ECG changes are now shown to begin within 30 seconds after infusion of PAAP+ S. sanguis, followed by alterations in blood pressure and respiratory rate. These changes occurred intermittently over a 30-minute period and changed within one heartbeat to a normal pattern and suddenly back to abnormal. Intermittent ECG abnormalities were seen in 13 of 15 rabbits, including left axis deviation, ST-segment depression, preventricular contractions, alternans, and bigemnia. Dose-dependent thrombocytopenia, accumulation of 111Indium-labeled platelets in the lungs, and tachypnea also occurred. No changes occurred with the PAAp- strain. The data indicated that PAPP+ S. sanguis interacts with circulating platelets, inducing thromboemboli to cause the pulmonary and cardiac abnormalities. During periodontitis, therefore, PAAP+ S. sanguis and P. gingivalis bacteremia may contribute to the chance of acute thromboembolic events.
 ...
PMID:Dental plaque, platelets, and cardiovascular diseases. 972 99

Oral bacteria exhibit highly specific adherence mechanisms and as a result they colonize and cause disease principally in the oral cavity. Oral pathogens, however, can produce systemic disease and are known causative agents of infective endocarditis. Recent studies have revealed that periodontal disease per se is also a statistically significant risk factor for cardiovascular disease. A link between the two diseases is the secretion and systemic appearance in periodontitis of pro-inflammatory cytokines capable of eliciting effects associated with atherosclerosis and coronary heart disease.
 ...
PMID:Oral pathogens: from dental plaque to cardiac disease. 1006 62

In most countries, coronary heart disease is one of the leading causes of morbidity and death. This report reviews the current evidence indicating that oral conditions (specifically periodontitis) may be a risk factor for atherosclerosis and its clinical manifestations and provides new preliminary data. This review is done in the context of the research indicating that inflammation plays a central role in atherogenesis and that there is a substantial systemic microbial and inflammatory burden associated with periodontal disease. Our review concentrates on 5 longitudinal studies that show oral conditions being associated with the onset of coronary heart disease while controlling for a variety of established coronary heart disease risk factors. In addition to published evidence, preliminary findings from our Dental Atherosclerosis Risk in Communities study also indicate that periodontal disease is associated with carotid intimal-medial wall thickness, a measure of subclinical atherosclerosis, adjusting for factors known to be associated with both conditions.
 ...
PMID:Dental infections and atherosclerosis. 1053 66

The early reports of a linkage between periodontitis and atherosclerosis have garnered further support by additional data generated by several investigative teams in many different countries. The evidence continues to suggest that periodontitis may be an important risk factor or risk indicator for cardiovascular pathology for some individuals. The term periodontitis-atherosclerosis syndrome (PAS) is proposed as a new diagnostic term to describe this condition in these individuals. Current evidence, albeit preliminary in nature, which describes a cluster of clinical signs and symptoms that are associated with this condition, is presented. It is clear that this syndrome will require considerable study and refinement before a definitive diagnosis and treatment plan can be formulated. Potential mechanisms by which systemic inflammation and infectious challenge of periodontal origin may serve as a potential modifier of cardiovascular disease are discussed in the context of a detailed working model of pathogenesis. This hypothetical model embraces many cellular and molecular components of atherogenesis and thromboembolic diseases from the perspective of periodontitis pathogenesis. Many aspects of the hypothetical model remain unproved; however, it is our opinion that only through the clarification of the mechanisms of pathogenesis can we ultimately construct a knowledge framework for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on the cardiovascular system represents an unprecedented challenge to our profession.
 ...
PMID:Periodontitis-atherosclerosis syndrome: an expanded model of pathogenesis. 1068 59

An epidemiological association between periodontitis and cardiovascular disease has been reported in multiple studies. Various mechanisms have been proposed as potential explanations for this association, including a common factor that predisposes certain individuals to a hyper-responsive inflammatory response. Variations in the genes that regulate the interleukin-1 (IL-1) response have been associated with both periodontal disease and cardiovascular disease. New data indicate that one pattern of IL-1 genetic polymorphisms, characterized by the IL-1A (+4845) and IL-1B (+3954) markers, is associated with periodontitis but not certain measures of atherosclerosis. Another IL-1 genetic pattern, characterized by the IL-1B (-511) and IL-1RN (+2018) markers, is associated with atherosclerotic plaque formation, as measured by angiography and arterial wall thickness, but not periodontitis. These two patterns also have different functional implications relative to IL-1 biological activity. Studies of IL-1 gene polymorphisms, atherosclerotic plaque instability and cardiovascular clinical events are in progress. Hypothetical models are presented to explain how IL-1 genetic factors may be involved in cardiovascular disease.
 ...
PMID:Interleukin-1 genotypes and the association between periodontitis and cardiovascular disease. 1068 60

Cardiovascular disease is the leading cause of death in developed countries. The cause is multifactorial. A substantial proportion of patients with coronary artery disease (CAD) do not have traditional risk factors. Infectious diseases may play a role in these cases, or they may intensify the effect of other risk factors. The association of CAD and Chlamydia pneumoniae infection is firmly established, but causality is yet to be proven. The link with other infectious agents or conditions, such as cytomegalovirus, herpes simplex virus, Helicobacter pylori and periodontitis, is more controversial. Cytomegalovirus infection is more strongly linked than native CAD to coronary artery restenosis after angioplasty and to accelerated CAD after cardiac transplantation. However, new data on this topic are appearing in the literature almost every month. The potential for novel therapeutic management of cardiovascular disease and stroke is great if infection is proven to cause or accelerate CAD or atherosclerosis. However, physicians should not "jump the gun" and start using antibiotic therapy prematurely for CAD. The results of large randomized clinical trials in progress will help establish causality and the benefits of antimicrobial therapy in CAD.
 ...
PMID:Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. 1092 Jul 32


1 2 3 4 5 6 7 8 9 10 Next >>