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)

To evaluate whether atherosclerosis may be associated with altered leucocyte rheology, we assessed leucocyte count (by Coulter counter), aggregation (by means of the leukergy test) and expression of adhesion molecules integrin LFA-1 and CD 44 (by means of immunofluorescence staining and flow cytometry) in 9 patients with carotid plus lower limb artery atherosclerosis (group A), 14 patients with carotid atherosclerosis only (group B) and 23 controls without atherosclerosis (group C). The level of LFA-1 (calculated as mean fluorescence channels-MFCs) on neutrophils, lymphocytes and monocytes was significantly higher (p < 0.05) in group A and B patients than in controls (group A-mean +/- SE: 383.77 +/- 9.42 vs 295.45 +/- 5.76; 474.22 +/- 8.86 vs 388.35 +/- 7.84; 457.66 +/- 12.03 vs 396.25 +/- 4.37. Group B: 322.42 +/- 6.36 vs 295.45 +/- 5.76; 421.42 +/- 7.21 vs 388.35 +/- 7.84; 415.71 +/- 7.73 vs 396.25 +/- 4.37, respectively); furthermore, the MFC of LFA-1 on neutrophils was significantly different (p < 0.05) between group A and B patients. The percentage of aggregated leucocytes was significantly higher (p < 0.05) in group A patients (4.46 +/- 1.07) than those in groups B (1.75 +/- 0.38) and C (1.43 +/- 0.25), whereas no significant difference was detected between groups B and C. Leucocyte number and expression of CD44 were not significantly different among the 3 groups. In conclusion, changes in leucocyte rheology are present in patients with atherosclerosis and may contribute to chronic ischaemia.
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PMID:Leucocyte rheological properties are altered in patients with diffuse atherosclerosis. 924 34

The adherence of blood monocytes to the endothelium, followed by transmigration beneath the endothelium, are initiating events in the formation of foam cells, promoting atherogenesis. We showed that adhesion molecules on leukocytes were up- or down-regulated in atherosclerosis, when binding of monoclonal antibodies was measured by indirect immunofluorescence with flow cytometry. Expression of PE-CAM-1 (CD31) on monocytes and LFA-1 (CD11a) on lymphocytes was increased with age. Expression of PECAM-1 in monocytes was also up-regulated in patients with coronary artery disease. Being unchanged on aging, expression of HAR (CD44) on polymorphonuclear leukocytes and monocytes was increased in patients with coronary artery disease. On the other hand, expression of L-selectin (CD62L) on polymorphonuclear leukocytes, and LFA-1, CR3 (CD11b) and VLA-4 (CD49d) on monocytes was decreased. These findings may show the mechanism of increased chemotaxis of monocytes beneath the endothelium during the incipient stage of atherosclerosis.
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PMID:[Adhesion of leukocytes to endothelial cells in atherosclerosis]. 986 1

Apoptotic macrophages are regularly found in atherosclerotic plaques indicating programmed cell death as one of their regulatory controls. The objective of this study was to characterize in more detail apoptotic macrophages in atherosclerotic lesions of humans and heritable hyperlipidemic (HHL) rabbits. Macrophages were immunohistochemically analyzed using antibodies directed against alphaMbeta2-integrins (CD11b/CD18), CD44, major histocompatibility complex (MHC) class I and II, inducible nitric oxide synthase (iNOS), manganese superoxide dismutase (MnSOD), tumor necrosis factor alpha (TNFalpha), p53, c-jun/AP-1 and rabbit macrophages (RAM-11) and the TUNEL (TdT-mediated dUTP nick end labeling) technique. Colocalization studies of human atherosclerotic carotid and aortic tissue showed apoptotic plaque macrophages also being MnSOD-, alphaMbeta2-integrin-, CD44-, MHC class I- and II-, iNOS-, TNFalpha- and p53-immunoreactive. Similar results occurred in atherosclerotic aortas of HHL rabbits. Computer-assisted morphometric analyses revealed a positive correlation of the area density of MnSOD-immunoreactive macrophages with those of alphaMbeta2-integrin- and CD44-immunoreactive ones, but not with those of MHC class I- and II- as well as of RAM-11-immunoreactive macrophages. We conclude that apoptotic macrophages located in atherosclerotic vessel wall are activated, antigen-presenting, integrin-expressing and oxidatively stressed cells. Since all these processes have been demonstrated to cause apoptosis of macrophages in vitro, we propose their potency accelerates the susceptibility of the macrophages to programmed cell death in atherosclerotic lesions.
Atherosclerosis 1999 May
PMID:Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits. 1038 Dec 75

Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50-70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic" state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms.
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PMID:The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation. 1158 4

The effect of hypercholesterolemia on the number, immunological phenotype and oxidative stress-dependent processes of macrophages (MPhi) and dendritic cells (DC) was studied in New Zealand White rabbits. The left ventricular myocardium was immunohistochemically analyzed in group I (control), which was on standard chow, and groups II and III, which both received a 0.5% cholesterol-enriched diet for 96 days, but thereafter, only group III was fed standard chow for 4 months. In the myocardial interstitium of group I, (1) significantly less RAM-11-immunoreactive (ir) MPhi than S-100-ir DC were found; (2) both, MPhi and DC, were similar major histocompatibility complex (MHC) class II molecules LN3-, ISCR3-, and 2.06-ir; (3) all MPhi and most DC were manganese superoxide dismutase (MnSOD)-ir and homing receptor CD44-ir. In group II, only MPhi increased about 10-fold in the myocardium in parallel to the about 40-fold increase of the serum cholesterol levels. In group III, the elevated serum cholesterol levels significantly decreased (about 90%), while the MPhi still remained significantly increased (about 8-fold). The cellular immunoreactivities of MHC class II molecules, as well as MnSOD and CD44 did not change in groups II and III in comparison to group I. We suggest that mainly the MPhi, which increase within the myocardium of rabbits after elevation of serum cholesterol levels and remain significantly increased for a long time after decrease of the blood lipid levels, might initiate or aggravate eventual complications such as coronary atherosclerosis and myocardial fibrosis.
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PMID:Hypercholesterolemia-induced long-term increase of macrophages in the myocardium of New Zealand White rabbits. 1450 29

The effect of infection with Chlamydia pneumoniae on host messenger RNA expression in human monocytic cells with complement DNA microarrays was studied. The data chronicle a cascade of transcriptional events affecting 128 genes, many of which have not previously been reported to be affected by C. pneumoniae infection. Down-regulated genes are primarily associated with RNA and DNA metabolism, chromosomal stability, and cell-cycle regulation. Up-regulated messages include those for a variety of genes with important proinflammatory functions. Many of the up-regulated genes-including the hyaluron receptor CD44, vasoconstrictor endothelin-1, smooth muscle growth factor heparin-binding EGF-like growth factor, and fatty acid binding protein-4-had been previously described as linked to the development of atherosclerosis and other chronic inflammatory diseases. C. pneumoniae-infected monocytes can contribute to the development and progression of diseases for which acute or chronic inflammation has been shown to be important, such as atherosclerosis.
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PMID:Infection of U937 monocytic cells with Chlamydia pneumoniae induces extensive changes in host cell gene expression. 1459 87

One of the major characteristics of atherosclerosis is the migration of smooth muscle cells (SMC) from the tunica media to the intima, caused by alterations in the environment, e.g. mechanical, chemical, or immunologic injuries of the arterial walls. A group of molecules that may act as a main regulator of SMC phenotype switching is formed by the so-called HMGA1 high-mobility group proteins. One target gene of the HMGA1 protein, playing a major role in the development of atherosclerotic lesions, is CD44. The expression of CD44 is regulated by IL-1beta, but binding of HMGA1 potentiates the transactivation of the CD44 promoter. In this study, the HMGA1 expression of human atherosclerotic plaque samples was examined. Compared to the non-active components, all major components of the well-developed atherosclerotic plaques showed strong positivity of the high-mobility group protein HMGA1 in their activated areas, e.g. neointimal SMCs, macrophages, newly built blood vessels. This report is the first to describe HMGA1 as one of the first mediators in the development of human atherosclerotic plaques.
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PMID:HMGA1 proteins in human atherosclerotic plaques. 1590 Nov 30

The pathogenesis of atherosclerosis, which remains the most important reason of mortality, is not well understood. Its present conception includes recruitment of inflammatory cells to the vessel wall, activation of vascular smooth muscle cells and endothelium. Much evidence indicate that CD44 molecule, the main receptor for hyaluronan, takes part in pathogenesis via several mechanisms. It mediates in lymphocyte T and monocyte adhesion to the endothelium, stimulates proinflammatory cytokine release from macrophages and participates in dedifferentiation phenotype of smooth muscle cells from contractile state to synthetic one. Furthermore CD44 acts in atherosclerotic plaque destabilization and neointimal proliferation after percutaneous vascular interventions. Numerous studies have supported the concept that CD44 participates in many stages of atherosclerosis. These studies suggest that inhibition of CD44 function may provide an effective mean for inhibiting atherosclerosis, but we still need further investigations for possible therapeutic implications.
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PMID:[The role of CD44 in pathogenesis of atherosclerosis]. 1637 26

Osteopontin (OPN) and CD44 have been implicated in the development of autoimmune diseases, including arthritis and multiple sclerosis, as well as chronic inflammatory diseases, such as atherosclerosis and colitis. To investigate their roles in autoimmune myocarditis induced by immunization with heart alpha-myosin (MyHC-alpha), a mouse model of human cardiomyopathy, we analyzed mice lacking OPN or CD44v6/v7, a CD44 isoform that binds OPN. Both, OPN(-/-) and CD44v6/v7(-/-) mice developed myocarditis with the same prevalence and severity as BALB/c wild-type controls. Furthermore, treatment of BALB/c mice with a pan-neutralizing anti-CD44 antibody did not affect the disease outcome. Consistently, expansion of MyHC-alpha-specific autoimmune CD4(+) T cells and MyHC-alpha autoantibody responses from either CD44v6/v7(-/-) mice or OPN(-/-) mice was indistinguishable from their wild-type controls. Thus, OPN and CD44v6/v7 are merely spectators rather than protagonists in autoimmune myocarditis.
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PMID:The osteopontin - CD44 pathway is superfluous for the development of autoimmune myocarditis. 1640 10

Closure of the ductus arteriosus (DA) is due to functional constriction followed by wall remodeling, with neointimal formation caused by proliferation and migration of smooth muscle cells (SMCs) from the media to subendothelium. CD44 is a surface cell proteoglycan family. Its isoform, CD44-v6, is only minimally expressed in SMCs in the media of normal arteries, but is highly expressed in SMCs in the intima and media of injured arteries (e.g., atherosclerosis). Twenty-two autopsy DA specimens, 11 from full-term babies (age range 2 days to 5 months) and 11 from premature babies (age range 3 days to 5 months), with varying degrees of ductal wall remodeling, were evaluated by immunohistochemistry using antiactin, antifibronectin-extradomain A, anti-leukocyte common antigen, anti-CD44, and anti-CD44-v6. In DA with wall remodeling, synthetic antifibronectin-extradomain A-positive SMCs were evident at the neointimal mounds, and the SMCs were highly positive for the CD44-v6 isoform, irrespective of gestational age at birth. Conversely, SMCs of either closed DAs or persistently patent DAs were CD44-v6 negative. In conclusion, the present data provide evidence that closure of DA involves synthetic SMCs highly positive for CD44-v6, and patent or closed DAs are populated by CD44-v6-negative SMCs.
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PMID:CD44-v6 expression in smooth muscle cells in the postnatal remodeling process of ductus arteriosus. 1692 69


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