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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The question why low-density lipoprotein (LDL) stranded in the subendothelium of arteries should acquire the proinflammatory properties that initiate and sustain atherogenesis has puzzled researchers for decades. The most popular concept contends that oxidative processes are crucial because oxidized LDL (ox-LDL) produced in vitro has atherogenic properties and small amounts of it are found in atherosclerotic lesions. Recently, a possible role for vascular infections has also been considered because infectious agents, in particular Chlamydia pneumoniae, are sometimes present in the lesions. Here, evidence is summarized for a different concept of atherogenesis, which evolves from the fact that nonoxidative, enzymatic degradation of LDL transforms the lipoprotein to an atherogenic moiety. Our group proposes that enzymatically degraded LDL (E-LDL) initiates and sustains atherosclerosis through its capacity to activate complement and macrophages. These processes are initially meaningful because they enable the stranded lipoprotein to be removed from the vessel wall, but they become harmful when the cholesterol removal system is overloaded. A novel type of chronic inflammation then ensues producing the characteristic pathology of the atherosclerotic lesion.
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PMID:Complement and atherogenesis: the unknown connection. 992 Mar 50

The aim of this study was to assess the presence of Chlamydia pneumoniae antibodies in patients with angiographically verified atherosclerotic coronary artery disease. A total of 114 consecutive patients were investigated between April 1995 and June 1996. Patients were divided into two groups: 72 patients with acute myocardial infarction (AMI; 53 men, 19 women, mean age 62.27 +/- 10.1 years), and 42 patients with chronic ischemic heart disease (CAD; 37 men, 5 women, mean age 62.75 +/- 9.2 years). A control group of 50 normal subjects matched for age (mean 62 +/- 9 years), sex, social status and geographical area was used. Identification of Chlamydia pneumoniae was carried out with the microimmunofluorescence method, on two serum samples taken from patients on admission and after 15 days. The IgM, IgG and IgA anti-Chlamydia pneumoniae titers were assessed, values > or = 1:16, > or = 1:32 and > or = 1:8 being respectively considered positive. Acute (IgM > or = 16 or four fold rise of IgG titer) and chronic (IgG > or = 128 e IgA > or = 32 or only elevated IgA titer) infections were analyzed. IgM antibodies were not found in AMI, CAD and control groups. IgG positivity (IgG > or = 32) was found in 38% of the control group, in 58.3% of the AMI group (p < 0.05) and 42.8% of the CAD group (p < 0.01). IgA positivity > or = 8) was found in 22% of the control group, in 31.9% of the AMI group (NS) and in 33.3% of the CAD group (p < or = 0.05). Acute infection was observed in 5.5% of AMI patients and in 12% of CAD patients (NS), whereas no subject of the control group showed these values. Chronic infection was observed in 9.7% of AMI patients and in 16.6% of CAD patients (NS) whereas nobody of the control group showed these values. In conclusion, our results suggest that Chlamydia pneumoniae infection is present only in the AMI and CAD groups. It is possible to suppose that this infection may be linked to atherosclerosis through an endothelial damage or a systemic endogenous procoagulant and inflammatory activity.
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PMID:[Chlamydia pneumoniae infection and cardiac ischemic syndromes]. 992 69

Helicobacter pylori infection is probably one of the most widely spread infectious diseases in man and a growing body of knowledge provides evidence in favour of a causal link between this infection and the majority of upper gastrointestinal conditions. For example, we now know that peptic ulcer disease is an infectious disease; if the infection is diagnosed and treated, ulcer can be cured. On the other hand, in recent years, a number of epidemiological studies have focused on the possible relation between ischaemic heart disease and several infectious disorders, such as chronic dental infections, Cytomegalovirus, Coxsackie viruses, Chlamydia and, finally Helicobacter pylori. The results of studies on the association between ischaemic heart disease and Helicobacter pylori have, in particular, often been contradictory, and only some studies adjusted the results for confounding factors, and the adjustment of the results in some cases modified the association. In conclusion, even if coronary atherosclerosis may now be considered as an inflammatory process, according to several histologic and pathophysiologic studies, we cannot, for the moment, be sure that it is an infectious disease.
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PMID:Helicobacter pylori infection and ischaemic heart disease. 1007 60

The vascular endothelium is the inner lining of all blood vessels and serves as an important autocrine and paracrine organ, that regulates vascular wall functions. Because of its strategic location between the circulating blood and the vascular wall, the endothelium interacts with cellular and neurohumoral mediators, thus controlling vascular contractile state and cellular composition. The vascular endothelium maintains vascular homeostasis by modulating blood vessel tone, by regulating local cellular growth and extracellular matrix deposition and by controlling hemostatic as well as inflammatory responses. One of the best characterized and most important substances released from the endothelium is nitric oxide (NO). NO is a soluble gas which is continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutively expressed nitric oxide synthase. The most important stimuli represent physical factors such as shear stress and pulsatile stretching of the vessel wall as well as circulating and locally released vasoactive substances. The endothelium can be seen as a biosensor, reacting to a large variety of stimuli and therefore maintaining adequate NO release. A large number of risk factors for atherosclerosis including hypercholesterolemia, systemic hypertension, smoking and diabetes have been associated with impaired endothelial NO-mediated vasodilation. "Endothelial dysfunction" is an early marker of atherosclerosis and may be closely related to the disease process. In acute coronary syndromes dysfunctional endothelium may trigger the devastating event of plaque rupture by promoting adhesion of leukocytes, vasoconstriction, activation of platelets and thrombos formation. Atherosclerotic blood vessels are further characterized by activation through zytokines and expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (E-Selectin). After adhesion to the endothelium mononuclear cells migrate to the subendothelial space to take up oxidized LDL, thus transforming into foam cells, a hall mark of early atherosclerotic lesions. A number of conditions including infection with Chlamydia pneumoniae may cause continuous activation of the endothelium and inflammation of the vessel wall. Continuous endothelial dysfunction and activation, caused by risk factors and infection, represent the basis for atherogenesis and acute coronary syndromes.
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PMID:[Endothelial dysfunction--assessment of current status and approaches to therapy]. 1009 15

Chlamydia pneumoniae is an important human respiratory pathogen. Recently, seroepidemiological data and the demonstration of chlamydial DNA or antigen within parts of atherosclerotic lesions have suggested a causal association between chlamydial infections and atherosclerosis. As the results obtained by different groups show considerable variations, we provide further data based on a highly specific and sensitive nested PCR method. Positivity was confirmed by nonradioactive hybridization with a specific probe, and sensitivity was determined by titration experiments. C. pneumoniae DNA was detected in 8/29 (28%) of carotid artery samples and 3/14 (21%) of aortic aneurysms.
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PMID:Detection of Chlamydia pneumoniae DNA in atheromatous tissues by polymerase chain reaction. 1019 48

Chlamydia are obligate intracellular eubacteria that are phylogenetically separated from other bacterial divisions. C. trachomatis and C. pneumoniae are both pathogens of humans but differ in their tissue tropism and spectrum of diseases. C. pneumoniae is a newly recognized species of Chlamydia that is a natural pathogen of humans, and causes pneumonia and bronchitis. In the United States, approximately 10% of pneumonia cases and 5% of bronchitis cases are attributed to C. pneumoniae infection. Chronic disease may result following respiratory-acquired infection, such as reactive airway disease, adult-onset asthma and potentially lung cancer. In addition, C. pneumoniae infection has been associated with atherosclerosis. C. trachomatis infection causes trachoma, an ocular infection that leads to blindness, and sexually transmitted diseases such as pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and epididymitis. Although relatively little is known about C. trachomatis biology, even less is known concerning C. pneumoniae. Comparison of the C. pneumoniae genome with the C. trachomatis genome will provide an understanding of the common biological processes required for infection and survival in mammalian cells. Genomic differences are implicated in the unique properties that differentiate the two species in disease spectrum. Analysis of the 1,230,230-nt C. pneumoniae genome revealed 214 protein-coding sequences not found in C. trachomatis, most without homologues to other known sequences. Prominent comparative findings include expansion of a novel family of 21 sequence-variant outer-membrane proteins, conservation of a type-III secretion virulence system, three serine/threonine protein kinases and a pair of parologous phospholipase-D-like proteins, additional purine and biotin biosynthetic capability, a homologue for aromatic amino acid (tryptophan) hydroxylase and the loss of tryptophan biosynthesis genes.
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PMID:Comparative genomes of Chlamydia pneumoniae and C. trachomatis. 1019 88

The role of inflammatory mechanisms in the initiation, progression and clinical expression of atherosclerosis is increasingly appreciated. With this awareness, the possibility that acute or chronic infection may initiate or modulate these processes in an active area of investigation. Infectious organisms may influence the atherosclerotic process through direct local effects on the coronary endothelium, on vascular smooth muscle cells and on macrophages in the atherosclerotic lesion. Infection may also exert systemic effects by inducing the elaboration of cytokines, the creation of a hypercoagulable state and by activating monocytes, causing possible transmission of infectious material to atherosclerotic lesions. Macrophages may then elaborate multiple mediators which destabilise plaque, promoting rupture and progression. Seroepidemiological data have identified associations between clinically active atherosclerosis and evidence of infection with Helicobacter pylori, Chlamydia pneumoniae and some herpesviridae. In addition, pathological examinations have demonstrated the presence of infectious organisms in coronary artery plaques. Cytomegalovirus, for example, has been identified pathologically to be associated with transplant vasculopathy and with an increased risk of restenosis following coronary intervention. Finally, recent pilot trials have demonstrated that macrolide antibacterial treatment directed against C. pneumoniae reduces the risk of recurrent coronary events. Infectious organisms may therefore influence atherogenesis through multiple pathways, and pathological and seroepidemiological investigations provide evidence of this association. Future large-scale clinical trials are needed to further evaluate the evidence of causality and the efficacy of antibacterial therapy for coronary artery disease.
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PMID:Antibiotics for myocardial infarction? A possible role of infection in atherogenesis and acute coronary syndromes. 1019 83

Recent investigations allow a controversial but convincing interpretation of the pathogenesis of atherosclerosis (arteriosclerosis). Atherosclerosis can be apparently the result of ultrachronic persistent infection by Chlamydia pneumoniae and not the result of heterogenous risk factors. The main arguments for the chlamydial genesis are: Correlation of coronary heart disease and other atherosclerotic diseases and antibodies against Chlamydia pneumoniae. Chlamydia pneumoniae could be detected with different techniques (PCR, ICC, immunohistology, electromicroscopy, culture) in a high percentage in atheromas from different sites. Three successful international studies with macrolides in coronary heart disease. Target cells of atherosclerosis (endothelia, macrophages, muscle cells) can be infected by Chlamydia pneumoniae in vitro. Provocation of an arteriitis in animal experiments. The reduction of incidence of atherosclerotic diseases since the 1960s, probably due to advanced antibiotic therapy. Elevated acute-phase proteins and other inflammatory signs (CRP, WBC count, fibrinogen) briefly before occurrence of myocardial infarction. There are good arguments for intervention studies in coronary heart disease and other manifestations of atherosclerosis. The relevant antibiotics are licensed for chlamydial infections, cheap and safe. Meticulous records and long-term observation of patients need to be developed, sometimes contrary to interests of the pharmaceutical industry.
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PMID:[Atherosclerosis--a chronic infectious disease caused by Chlamydia pneumoniae]. 1020 Jun 11

Chlamydia pneumoniae is an important respiratory pathogen. Recently, its presence has been demonstrated in atherosclerotic lesions. In this study, we characterized C. pneumoniae-mediated activation of endothelial cells and demonstrated an enhanced expression of endothelial adhesion molecules followed by subsequent rolling, adhesion, and transmigration of leukocytes (monocytes, granulocytes). These effects were blocked by mAbs against endothelial and/or leukocyte adhesion molecules (beta1 and beta2 integrins). Additionally, activation of different signal transduction pathways in C. pneumoniae-infected endothelial cells was shown: protein tyrosine phosphorylation, up-regulation of phosphorylated p42/p44 mitogen-activated protein kinase, and NF-kappaB activation/translocation occurred within 10-15 min. Increased mRNA and surface expression of E-selectin, ICAM-1, and VCAM-1 were noted within hours. Thus, C. pneumoniae triggers a cascade of events that could lead to endothelial activation, inflammation, and thrombosis, which in turn may result in or may promote atherosclerosis.
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PMID:Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae. 1020 27

Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that causes acute upper and lower respiratory infections. Its distribution is worldwide. Seroepidemiological studies have shown an association between C. pneumoniae and atherosclerosis, and the risk of acute myocardial infarction. Several studies had detected C. pneumoniae in atherosclerotic lesions from coronary and carotid arteries, in abdominal aortic aneurysms (AAA), and in sclerotic aortic valves. One study consistently succeeded in culturing C. pneumoniae from an atherosclerotic lesion, indicating the presence of viable organisms. However, the pathogenicity is unknown, and the significance of detecting the organism is unresolved. In two minor controlled clinical trials, patients with ischaemic heart disease were randomised into antibiotic-treated and placebo groups. Both trials showed a significant reduction in serious endpoints in patients receiving macrolide. Macrolide therapy thus seems to improve the outcome of severe ischaemic heart disease. It is not known whether this is caused by eradicating C. pneumoniae organisms, or by the macrolide's non-specific anti-inflammatory effect. Since both C. pneumoniae and inflammation are found in the AAA wall, it may be considered that macrolide would also improve the outcome of AAA and other diseases related to vascular surgery. In order to confirm this, randomised trials with macrolide therapy are needed, as well as diagnostic methods that can differentiate between individuals who are or are not infected with C. pneumoniae. The latter are needed in order to clarify the impact of the presence of C. pneumoniae and to avoid indiscriminate use of antimicrobials.
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PMID:A review of Chlamydia pneumoniae and atherosclerosis. 1020 48


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