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 by human cytomegalovirus (HCMV) is associated with the development of vascular diseases and may cause severe brain damage in infected fetuses. Platelet-derived growth factor receptors alpha and beta (PDGFR-alpha and -beta) control important cellular processes associated with atherosclerosis and fetal development. In the present investigation, our goal was to determine whether infection by HCMV can influence the expression of PDGFR-alpha and -beta in human smooth muscle cells (SMCs). In connection with HCMV infection in vitro the levels of PDGFR-alpha and -beta at the cell surface and in the total cellular protein of SMCs were reduced in parallel with decreases in the levels of the corresponding mRNAs. These effects were dependent on immediate-early (IE) or early (E) HCMV gene products, since inhibition of late genes did not prevent HCMV from affecting the expression of PDGFR-alpha and -beta. The downregulation of PDGFR caused by HCMV was dose dependent. Furthermore, confocal microscopy revealed that the localization of PDGFR-beta was altered in HCMV-infected cells, in which this protein colocalized with proteins associated with endosomes (Rab4 and -5) and lysosomes (Lamp1 and -2), indicating entrance into pathways for protein degradation. Altogether these observations indicate that an IE and/or E HCMV protein(s) downregulates the expression of PDGFR-alpha and -beta in SMCs. This phenomenon may disrupt cellular processes of importance in connection with cellular differentiation, migration, and/or proliferation. These observations may explain why congenital infection with HCMV can cause fetal brain damage.
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PMID:Human cytomegalovirus downregulates expression of receptors for platelet-derived growth factor by smooth muscle cells. 1734 84

Infection with bacteria such as Chlamydia pneumonia, Helicobacter pylori or Porphyromonas gingivalis may be triggering the secretion of inflammatory cytokines that leads to atherogenesis. The mechanisms by which the innate immune recognition of these pathogens could lead to atherosclerosis remain unclear. In this study, using human vascular endothelial cells or HEK-293 cells engineered to express pattern-recognition receptors (PRRs), we set out to determine Toll-like receptors (TLRs) and functionally associated PRRs involved in the innate recognition of and response to lipopolysaccharide (LPS) from H. pylori or P. gingivalis. Using siRNA interference or recombinant expression of cooperating PRRs, we show that H. pylori and P. gingivalis LPS-induced cell activation is mediated through TLR2. Human vascular endothelial cell activation was found to be lipid raft-dependent and to require the formation of heterotypic receptor complexes comprising of TLR2, TLR1, CD36 and CD11b/CD18. In addition, we report that LPS from these bacterial strains are able to antagonize TLR4. This antagonistic activity of H. pylori or P. gingivalis LPS, as well as their TLR2 activation capability may be associated with their ability to contribute to atherosclerosis.
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PMID:Lipopolysaccharides from atherosclerosis-associated bacteria antagonize TLR4, induce formation of TLR2/1/CD36 complexes in lipid rafts and trigger TLR2-induced inflammatory responses in human vascular endothelial cells. 1741 16

Atherosclerosis is a chronic inflammation and the cause of most cardiovascular diseases. It is the main cause of death in the Western world today, even though growing incidence of atherosclerosis-related diseases has been recently observed in developing countries, too. In many patients with atherosclerosis, however, traditional risk factors for atherosclerosis are not identifiable. This has renewed the interest, in recent years, in the links between atherosclerosis and environmental exposures, including infectious agents. Infection was identified as as risk factor for atherosclerosis in the first half of the 20th century. Experimental and clinical studies have shown that infection can stimulate atherogenic processes and that there are significant interactions between infection and traditional risk factors. Yet there are questions concerning etiology, pathogenesis and appropriate interventions which remain unanswered. The following article provides an overview of the role of the infectious agents in atherosclerosis and discusses possible intervention strategies.
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PMID:[Infection and atherosclerosis]. 1750 40

Chlamydophila (Chlamydia) pneumoniae is an intracellular respiratory pathogen known to cause community-acquired pneumonia. Infection with this organism has been associated with atherosclerosis, inflammatory arthritis, and other chronic diseases, many of which also have been associated with possession of the epsilon4 allele at the APOE locus on (human) chromosome 19. An earlier study from this laboratory suggested that some relationship exists between apolipoprotein E4 (apoE4), the product of the epsilon4 allele, and the pathobiology of C. pneumoniae. A standard attachment assay and real time PCR targeting a sequence on the C. pneumoniae chromosome were used to monitor host cell binding of elementary bodies (EB) of that organism. Our data indicate that 3-fold more EB of strain AR-39 attach to an epsilon3 homozygous human cell line transfected with a plasmid expressing the epsilon4 coding sequence than to the same cell line harboring empty vector, vector containing an irrelevant insert sequence, or vector containing the DNA sequence encoding apoE3. The quantitative real time data were confirmed by immunolabeling of chlamydial inclusions in parallel attachment and infection assays. Experiments using Chlamydophila trachomatis EB showed no enhancement of attachment in the presence of the epsilon4 allele in any assays. These observations indicate that apoE4 enhances attachment of C. pneumoniae EB, but not those of C. trachomatis, to target host cells.
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PMID:Apolipoprotein E4 enhances attachment of Chlamydophila (Chlamydia) pneumoniae elementary bodies to host cells. 1799 73

The respiratory pathogen Chlamydophila pneumoniae can be detected in atherosclerotic vessels, but the mechanism of dissemination from lung to vasculature remains unknown. Disturbance of vascular shear stress is a risk factor for atherosclerosis. We investigated whether polymorphonuclear neutrophils (PMN) might serve as carriers, transmitting C. pneumoniae to endothelial cells and how this is affected by shear stress. PMN were prepared from blood and incubated with C. pneumoniae. Real-time PCR and Pathfinder staining showed that after 1h, 20% of C. pneumoniae were ingested and started to form inclusions. When infected PMN were co-incubated with HUVEC for 96h, 10% of PMN-ingested C. pneumoniae were transmitted to HUVEC as shown by PCR and confocal microscopy. Infection of HEp-2 cells with C. pneumoniae harvested from HUVEC resulted in C. pneumoniae replication and confirmed that the bacteria remained infective. Exposure to laminar shear stress in a rotating cone-and-plate apparatus did not affect the transmission of C. pneumoniae from PMN to HUVEC, but led to a 75% reduction of inclusion formation. This can explain the focal distribution of C. pneumoniae in the vasculature and links two risk factors of atherosclerosis, i.e. the lack of laminar flow and infection.
Atherosclerosis 2008 Jun
PMID:Endothelial cells are protected against phagocyte-transmitted Chlamydophila pneumoniae infections by laminar shear stress Gueinzius: Shear stress protects from C. pneumoniae infection. 1805 38

The aim of this study was to investigate the seroprevalence of Helicobacter pylori (HP) in patients with coronary atherosclerosis and acute coronary syndromes. We enrolled 152 patients (group I, 73 patients with acute coronary syndrome; group II, 79 patients with chronic stable angina) and 22 control subjects. An enzyme-linked immunosorbent assay for immunoglobulin (Ig) G test for HP diagnosis was used on all enrolled subjects. C-reactive protein (CRP) was also measured in all patients as an inflammatory marker. Seropositivity rates for HP were significantly higher in patients with coronary artery disease than in controls (80.2% versus 54.5%; P < 0.05). Although CRP level was significantly higher in group I than in group II (1.72 +/- 2.89 mg/dl versus 0.53 +/- 0.63 mg/dl, P < 0.0001), HP infection rates were similar between groups (86.3% versus 74.6%, P > 0.05). Infection with HP may influence atherogenesis through low-grade, persistent inflammatory stimulation. However, our data show evidence of increased systemic inflammation in patients with acute coronary syndrome, which was unrelated to an increased HP seropositivity.
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PMID:Helicobacter pylori seropositivity in patients with acute coronary syndromes. 1877 33

Infection and inflammation may have a crucial role in the pathogenesis of atherosclerosis. This hypothesis is supported by an increasing number of reports on the interaction between chronic infection, inflammation, and atherogenesis. Assessment of serological and inflammatory markers of infection may be useful adjuncts in identifying those patients who are at a higher risk of developing vascular events, and in whom more aggressive treatments might be warranted.
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PMID:Microbial risk factors of cardiovascular and cerebrovascular diseases: potential therapeutical options. 1901 3

Basic and animal research implicate inflammatory mechanisms in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers, particularly high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2, have been identified as potential predictors of stroke risk and prognosis. Infections may also precipitate stroke. Medications, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), reduce inflammatory marker levels independently of lipid effects, and the ability of statins to reduce coronary events and stroke correlates with their effect on inflammatory biomarkers. Vaccination against influenza may also reduce stroke risk. Determining whether reduction of biomarkers reduces risk of recurrent stroke, however, requires further study before inflammatory markers become a routine part of the evaluation of stroke patients.
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PMID:Inflammatory markers and stroke. 1909 Nov 70

The Center for Molecular Medicine (CMM) was conceived and built to respond to the challenges presented by the still common chronic diseases such as atherosclerosis, rheumatoid arthritis, diabetes, allergy, and alcoholism. The Karolinska University Hospital has a proud history of research with developments such as the pacemaker and the gamma-knife. The nearby Karolinska Institutet has a strong presence internationally on the basic sciences. However, the challenges of the "new biology" and the access to the complete human genome, transcriptome, and proteome raised the need for a new research institute that could meet the experimental requirements for translational research. A Foundation was established in 1994 with the goal to build and govern the new enterprise. After an intense fundraising campaign, building could start and CMM (Fig. 1) was inaugurated in 1997. Through more than 10 years of existence, it has evolved into a multidisciplinary research institute with research in four programs, Cardiovascular and Metabolic Diseases, Infection and Immunity, Neuropsychiatric Diseases, and Medical Genetics. Performance parameters have been introduced and scientific impact and relevance are followed annually. Transparency and collaboration between groups (now 28 groups with an approximate total of 400 people engaged in research) and leadership training for junior faculty are means to stimulate "centerness".
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PMID:At crossroads between laboratory disciplines and medical advancements-The Center for Molecular Medicine at the Karolinska University Hospital. 1931 99

The aim of this study was to identify the influence of diabetes mellitus on patients with atherosclerosis obliterans (ASO) of the lower extremities. A prospective study was designed to compare differences between ASO patients with and without diabetes mellitus in regard to clinical characteristics and outcomes of management. Two hundred fifty-three consecutive (61.1%) diabetic and 161 (38.9%) nondiabetic patients were included in this study. Crural artery occlusion occurred more frequently in diabetic patients (tibioperoneal segment 26.5% vs 14.3%; p = .003). Diabetic patients had higher comorbidities, such as ischemic heart disease, disabling stroke, and renal failure. Infection requiring urgent surgical intervention was higher in diabetic patients (39.1% vs 24.2%; p = .001). This required primary major amputation in limb-threatening ischemia superimposed with infection (27.6% vs 17.7%; p = .037). The feasibility (67.2% vs 69.8%; p = .651) and success (74.4% vs 79.0%; p = .481) of revascularization between the two groups were comparable. Diabetic patients often needed more distal revascularization for limb salvage (34.4% vs 18.5%; p = .019). The mortality rate after revascularization was higher in diabetic patients (13.3% vs 2.5%; p = .009). Diabetes mellitus per se has no direct impact on limb salvageability in limb-threatening ischemia. The parity of feasibility and success in revascularization between the two groups should encourage attempts at limb salvage revascularization in diabetic patients.
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PMID:Comparative study of the management of diabetic versus nondiabetic patients with atherosclerosis obliterans of the lower extremities. 1934 91


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