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)

Infection with the pathogens human cytomegalovirus (HCMV) or Chlamydia pneumonia (CP) is linked to the development of vascular disease, including atherosclerosis. The role of pathogens in vasculopathies has been controversial. However, animal models have demonstrated a direct link between infection with CP and herpesviruses and the development of vascular disease. Clinical studies have shown a direct association of HCMV and CP with the acceleration of vascular disease. This article will review the evidence supporting the role for CP and HCMV in the development of vascular disease and will suggest a potential mechanism for HCMV acceleration of the disease process. Vascular diseases are the result of either mechanical or immune-related injury followed by inflammation and subsequent smooth muscle cell (SMC) proliferation and/or migration from the vessel media to the intima, which culminates in vessel narrowing. A number of in vitro and in vivo models have provided potential mechanisms involved in pathogen-mediated vascular disease. Recently, we have demonstrated that HCMV infection of arterial but not venous SMC results in significant cellular migration in vitro. Migration was dependent on expression of the HCMV-encoded chemokine receptors, US28, and the presence of the chemokines, RANTES or MCP-1. Migration involved chemotaxis and provided the first evidence that viruses may induce migration of SMC toward sites of chemokine production through the expression of a virally encoded chemokine receptor in infected SMC. Because SMC migration into the neointimal space is the hallmark of vascular disease, these observations provide a molecular link between HCMV and the development of vascular disease.
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PMID:Do pathogens accelerate atherosclerosis? 1158 10

Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in atherosclerosis. Here we show that infection with C. pneumoniae protects HeLa human epithelioid cells against apoptosis induced by external stimuli. In infected HeLa cells, apoptosis induced by staurosporine and CD95-death-receptor signaling was strongly reduced. Upon treatment with staurosporine, generation of effector caspase activity, processing of caspase-3 and caspase-9 and cytochrome c redistribution were all profoundly inhibited in cells infected with C. pneumoniae. Bacterial protein synthesis during early infection was required for this inhibition. Furthermore, cytochrome c-induced processing and activation of caspases were inhibited in cytosolic extracts from infected cells, suggesting that a C. pneumoniae-dependent antiapoptotic factor was generated in the cytosol upon infection. Infection with C. pneumoniae failed to induce significant NF-kappaB activation in HeLa cells, indicating that no NF-kappaB-dependent cellular factors were involved in the protection against apoptosis. These results show that C. pneumoniae is capable of interfering with the host cell's apoptotic apparatus at probably at least two steps in signal transduction and might explain the propensity of these bacteria to cause chronic infections in humans.
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PMID:Characterization of antiapoptotic activities of Chlamydia pneumoniae in human cells. 1159 88

First recognized as a major determinant in lipoprotein metabolism and cardiovascular disease, apolipoprotein (apo) E has emerged as an important molecule in several biological processes not directly related to its lipid transport function, including Alzheimer's disease and cognitive function, immunoregulation, and possibly even infectious diseases. ApoE is a polymorphic protein arising from three alleles at a single gene locus. The three major isoforms, apoE4, apoE3, and apoE2, differ from one another only by single amino acid substitutions, yet these changes have profound functional consequences at both the cellular and molecular levels. ApoE3 seems to be the normal isoform in all known functions, while apoE4 and apoE2 can each be dysfunctional. Isoform (allele)-specific effects include the association of apoE2 with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis and the association of apoE4 with increased risk for both atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth; isoform-specific differences in cellular signaling events may also exist. Functional differences in the apoE isoforms that affect (or did affect) survival before the reproductive years probably account, at least in part, for the allele frequencies of the present day.
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PMID:Apolipoprotein E: far more than a lipid transport protein. 1170 39

Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study demonstrated the effects of gamma interferon (IFN-gamma)-mediated indoleamine 2,3-dioxygenase activity on C. pneumoniae persistence in HEp-2 cells, inclusion morphology, and ultrastructure. C. pneumoniae replication showed a dose-dependent decrease when treated with increasing concentrations of IFN-gamma and a phenotypic switch resulting in a decrease in typical inclusions with an increase in smaller, less-dense atypical inclusions. Ultrastructural analysis of IFN-gamma-treated C. pneumoniae revealed atypical inclusions containing large reticulatate-like aberrant bodies with no evidence of redifferentiation into elementary bodies.
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PMID:Characterization of Chlamydia pneumoniae persistence in HEp-2 cells treated with gamma interferon. 1170 79

Every other year the Keystone Symposia organizes a meeting to discuss the state of the art in chemokine and chemokine receptor research. The focus of the meeting in the past has included the structural and functional identification of chemokines and their receptors. However, this year there was heavy emphasis on the role of chemokines on normal immune function and disease pathogenesis. A number of exciting results were presented and discussed, for example the role of chemokines and chemokine receptors in development and progression of tumours, induction and progression of auto-immunity, development of atherosclerosis and the resolution of infectious disease. The last session of the meeting was devoted to discussion of chemokine and chemokine receptor antagonists currently in preclinical development or Phase I clinical trials.
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PMID:Keystone Symposia: chemokines and chemokine receptors. 16-21st February 2001, Taos, NM, USA. 1172 25

Recent evidence suggests that common chronic infections may contribute to the initiation and/or progression of atherosclerosis. Infection of the vascular wall with Chlamydia pneumoniae, a gramnegative bacterium, has been linked with coronary heart disease, myocardial infarction and stroke in epidemiological studies and in pathological studies using immunohistochemistry and electron microscopy. In addition striking evidence for an active role of Chlamydia pneumoniae in atherogenesis has been provided in animal models and from preliminary data of intervention trials. Although these observations strongly indicate an involvement of Chlamydia pneumoniae in the pathogenesis of atherosclerosis, a causal relationship has not been established yet. In the last years several interesting papers have dealt with the molecular mechanisms how an infection with Chlamydia pneumoniae affects the vascular wall to initiate or facilitate vascular dysfunction.
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PMID:[Chlamydia pneumoniae--chronic infection and atherosclerosis]. 1182 Jan 75

Seroepidemiologic studies have shown an association of Chlamydia pneumoniae antibody with atherosclerosis. Compelling additional evidence has accumulated, in that the organism has been found within atherosclerotic lesions throughout the arterial tree by multiple methods. C. pneumoniae has also been isolated from coronary and carotid atheromatous plaques. Although these studies support a potential role for C. pneumoniae in atherogenesis, confirmation of a causal relationship requires the use of animal models and intervention studies. We have focused on the evaluation of mouse models to address the hypothesis that, following upper respiratory tract infection, lung macrophages are infected, disseminate to the aorta, and alter the onset or progression of atherogenesis. ApoE-deficient knock-out and C57BL/6J mice were used. The apoE-deficient mouse develops atherosclerotic lesions spontaneously on a regular diet in a time- and age-dependent manner. This knock-out strain was developed on the background of the C57BL/6J mouse, which only develops atherosclerosis on a high-fat/high-cholesterol diet. To investigate whether infected macrophages constitute a vehicle for dissemination of C. pneumoniae in vivo, mice were inoculated intranasally or intraperitoneally. The organism was detected in harvested alveolar and peritoneal macrophages at all time points following intranasal and intraperitoneal inoculations, respectively, and in peripheral blood mononuclear cells following inoculation by both routes. In another experiment, alveolar and peritoneal macrophages from intranasally and intraperitoneally inoculated mice were adoptively transferred by intraperitoneal injection to uninfected mice. Subsequently, C. pneumoniae was detected in lung, spleen, abdominal lymph nodes and/or thymus of recipient mice. In control experiments, UV-inactivated C. pneumoniae DNA was not detected in alveolar or peritoneal macrophages beyond 5 min after inoculation in vivo. These cumulative results demonstrate that C. pneumoniae infects macrophages in vivo and that macrophages can serve as a vehicle for dissemination to other sites. To answer the question of whether the organism disseminates to and persists in the aorta, 8-week-old mice were infected intranasally. Following single or multiple inoculations in apoE-deficient mice, C. pneumoniae was detected in the lung and aorta for 20 weeks postinfection. In contrast, in C57BL/6J mice, the organism did not persist in the aorta following a single intranasal inoculation, but could be detected up to 7 weeks postinfection in multiply inoculated mice. Significantly, in apoE-deficient mice with developed atherosclerotic lesions, the organism was found in foam cells within the lesions by immunocytochemical staining. These studies show that persistent C. pneumoniae infection occurs in atherosclerotic lesions in the aorta in the apoE-deficient knock-out mouse model. Infection of the aorta also occurred in C57BL/6J mice but was more transient. Both models should be useful in studying the pathogenic role of C. pneumoniae in atherogenesis and for determining if therapy prevents dissemination of infection. To this end, we have evaluated the susceptibility of C. pneumoniae to roxithromycin, a new macrolide, in vitro in cell culture and in vivo in the apoE-deficient mouse model. In vitro results compare favorably with other new macrolides, quinolines, and tetracyline. Preliminary studies in the apoE model of persistent infection suggest that the organism is detected less frequently in the lung and aorta by PCR following treatment. These promising preliminary studies warrant further investigation.
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PMID:Preclinical models for Chlamydia pneumoniae and cardiovascular disease: hypercholesterolemic mice. 1186 67

CRP has long been used as a sensitive marker for infectious diseases. Since its serum concentration elevates more than 10 mg/dl with gram-negative bacterial infections, the sensitivity can be enough to be around 0.3-0.6 mg/dl for the diagnosis. However, the sensitivity should be higher in the early diagnosis of infections in new-borne babies. In addition, recently, it was suggested that atherosclerotic lesions are a kind of vasculitis, and the information could be transmitted via production of inflammatory cytokines and acute phase proteins. In fact, serum CRP and serum amyloid protein A(SAA) levels are elevated even in patients with coronary atherosclerosis without acute coronary syndrome(ACS). However, the level was much lower than the cut-off for diagnosis of bacterial infection. Therefore, the high-sensitive assay method has been applied. As the result, high-sensitivity(hs) CRP assay was found to be one of the most sensitive markers for prediction of future ACS in USA. Combination of hsCRP and atherogenic index such as total cholesterol/HDL cholesterol or LDL cholesterol/HDL cholesterol ratio is more useful. Similarly, it was found that hsCRP could predict the future prevalence of ACS even in Japan. It may be true because production of CRP is independent upon the genetic backgrounds. Early prevention of ACS by the measurement of hsCRP is calculated to be economic even if we measured hsCRF often in subjects without symptoms, because medical cost for treatment of acute myocardial infarction is enormous. In patients with high risk for coronary heart diseases, hsCRP-guided therapy is possible by using aspirin, stains, and antibiotics for prevention of ACS.
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PMID:[High-sensitivity C-reactive protein (CRP) assay--a novel method for assessment of risk ratios for atherosclerotic vascular diseases]. 1187 Nov 34

Diabetes mellitus has reached epidemic proportions worldwide as we enter the new millennium. The World Health Organization (WHO) has commented there is 'an apparent epidemic of diabetes which is strongly related to lifestyle and economic change'. Over the next decade the projected number will exceed 200 million, possibly reaching 250 million persons. Most will have type 2 diabetes and all are at risk of the development of complications. Better education, improved nutrition, more exercise, early diagnosis and prompt treatment are imperative. Diabetes is a serious disease, subject to the development of many complications affecting large vessels (heart, cerebral and peripheral), small vessels (kidney and retina), nerves and other organs. In type 2 diabetes these complications may precede diagnosis of the disease by many years. The process continues inexorably, with premature mortality and morbidity mainly from the development of vascular disease. Data from the WHO confirm the principal role of non-communicable disease on mortality in developed countries, while mortality in developing countries is rising rapidly, now often exceeding communicable disease. The non-communicable diseases are divided into cancer and degenerative diseases. In the developed world, degenerative diseases are grouped to include ischaemic heart disease, stroke, renal failure, hypertension and other macro- and microvascular diseases. The major complications of diabetes encountered most frequently and with the greatest impact are: 1. Neuropathy, both peripheral and autonomic, with principal manifestations in the lower limbs 2. Microvascular disease, mainly affecting the retina and kidney, resulting in blindness and renal failure 3. Macrovascular disease, presenting with atherosclerosis in the coronary arteries causing ischaemic heart disease, cerebrovascular disease causing stroke and peripheral vascular disease contributing to diabetic gangrene.
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PMID:The economic burden of insulin resistance. 1196 27

The established risk factors for atherosclerosis such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and hyperhomocysteinemia do not explain clinical and epidemiological features of coronary heart disease (CHD). The role of infectious disease as a CHD risk factor may partly explain these features. Chronic infection with various microorganisms, particularly, Chlamydia pneumoniae, Cytomegalovirus (CMV) and Helicobacter pylori may play a role in etiological factors, linking inflammation and atherogenesis. Results from epidemiological studies, pathology of atherosclerotic plaques, animal studies, molecular biology and clinical antibiotic trials indicated a positive association between C. pneumoniae infection and CHD. Chronic infection might also influence preexisting plaque by enhancing T cell activation, which participate in destabilization of intimal cap. However, the exact nature of pathophysiological link between the organisms and CHD remains to be elucidated. Future antibiotic interventional studies may help to further clarify the role of chronic infection and inflammation in CHD.
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PMID:Chronic infections and atherosclerosis. 1200 6


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