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 arterial conduits such as internal thoracic artery (ITA) and right gastroepiploic artery (GEA) are widely used in coronary artery bypass surgery because of their resistance to atherosclerosis. In this study, immunophenotypes of smooth muscle cells (SMCs) in intima and media of ITA, GEA and saphenous vein (SV) were studied using monoclonal antibodies specific to cytoskeletal proteins; actin (A), vimentin (V) and desmin (V). In addition, the ultrastructures of endothelium of these vessels were examined. The most SMCs in intima and media of ITA and GEA were found positive for (A) and (V) but negative for (D). In contrast, the majority of SMCs both in intima and media of SV were found positive for (A), (V) and (D). The ultrastructure of endothelium of ITA and GEA showed the deeper penetration of cytoplasmic process than SV, which might anchor the endothelium. We suggest the morphological difference of endothelium and phenotypic diversity of SMCs between arterial and venous grafts may account for the different susceptibility to atherosclerotic changes in coronary bypass grafting.
 ...
PMID:[Immunocytochemical and ultrastructural study of saphenous vein, internal thoracic artery, and right gastroepiploic artery in coronary artery bypass grafting]. 837 87

Circulating autoantibodies to various components of the arterial wall have been reported in atherosclerosis. To examine the occurrence of autoantibodies to cytoskeletal proteins in coronary artery disease (CAD) we studied 56 patients with angiographically demonstrable CAD and compared them with 37 controls without CAD. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum samples. In coronary patients, antibody absorbance values at least two standard deviations above the mean for the controls were considered positive. The following numbers of positive antibody absorbances were found in the group of 56 patients: actin IgG, 6 (10.7%); cytokeratin-18 IgG, 3 (5.4%), IgA, 2 (3.6%); myosin IgA, 11 (19.6%); desmin IgG, 13 (23.2%), IgM, 3 (5.4%); vimentin IgG, 2 (3.6%), IgM, 7 (12.5%), IgA, 6 (10.7%). The specificity of desmin IgG was tested with Western blotting against extracts of human internal mammary artery. The positive antibody absorbances to one or several cytoskeletal proteins in the patients were not found to correlate with the clinical symptoms of CAD. Our results suggest an association between autoantibodies to cytoskeletal proteins, particularly to those for desmin, with angiographically assessable CAD.
Atherosclerosis 1993 Jan 04
PMID:Antibodies to cytoskeletal proteins in sera of patients with angiographically assessed coronary artery disease. 845 45

Intimal cells play an important role in the biology of the vascular wall. Variability in the metabolic activity of intimal smooth muscle cells (SMC), as well as the differential expression of cellular cytoskeletal proteins depend on factors such as degree of differentiation, aging, atherosclerosis, etc. Myosin ATPase activity and cytoskeletal proteins were studied in the intima of bovine femoral arteries and veins of mature animals. In some arteries the intima was thickened and two distinct layers--inner elastic hyperplastic (EHL) and outer, musculo-elastic (MEL) were observed. ATPase activity was well defined in endothelial cells (EC) as well as in SMC. However, differential enzymatic expression was observed in thickened intimas. SMC in the EHL were ATPase negative, while in the MEL they were ATPase positive. All EC and SMC in the "normal" intimas were vimentin positive, desmin and cytokeratin negative. In vessels with thickened intimas, the EHL showed intensive vimentin positivity; in the MEL desmin immunoreactive SMC were numerous as were as those in the media. Vimentin-positive SMC occupied their innermost part. Differences in the expression of ATPase activity and cytoskeletal proteins is discussed in terms of possible migration of medial SMC and/or morphological modulation observed in vessels with altered vascular walls.
 ...
PMID:Expression of cytoskeletal proteins and ATPase activity in bovine femoral artery and vein intima. 886 55

This study was carried out to determine whether sympathectomy influences the phenotypic modulation of smooth muscle cells in the peripheral and cerebral arteries of heritable hyperlipidaemic rabbits. Unilateral superior cervical ganglionectomy (common origin of innervation to the middle cerebral artery and the central ear artery) was performed on four Watanabe heritable hyperlipidaemic rabbits. Cross-sections of the ipsi- (sympathectomized) and the contralateral (intact) cerebral and ear arteries were prepared 2 months later and labelled with monoclonal antibodies against vimentin and desmin, two markers of the differentiation of smooth muscle cells, and alpha-smooth muscle actin, a marker of these cells. Sections from control and sympathectomized arteries were analysed with a confocal laser scanning microscope. Compared with contralateral intact ear arteries, the sympathectomized ear artery developed a thickened intima with dedifferentiated smooth muscle cells, expressing alpha-smooth muscle actin but no desmin, whereas the middle cerebral artery remained unchanged. These results suggest that sympathectomy may favour the progression of atherosclerosis in peripheral but not in cerebral arteries of Watanabe heritable hyperlipidaemic rabbits.
 ...
PMID:Effect of sympathectomy on the phenotype of smooth muscle cells of middle cerebral and ear arteries of hyperlipidaemic rabbits. 918 42

There is an increasing interest in irradiation to control restenosis after balloon angioplasty by an internal radioactive source. Differences in radiosensitivity of the predominant cells of the human coronary artery (i.e. endothelial cells (HCAEC), smooth muscle cells from the media (HCMSMC) and from plaque material (HCPSMC), are issues of controversal discussion. Therefore, we investigated the graded inhibition of cells by irradiation from a balloon catheter filled with a high-energy beta-emitter (Rhenium-188) in vitro. HCPSMC, HCMSMC and HCAEC were cultured and irradiated with increasing dose from 7.5 to 37.5 Gy at a dose rate of 1.5+/-0.3 Gy/min. After irradiation, bromodeoxyuridine (BrdU) was added and cells were fixed 18 h later. In a limited field opposite to the balloon, the number of BrdU-positive cells were analysed in comparison to non-irradiated controls. Significant inhibition was demonstrated in HCPSMC and HCMSMC at 7.5 Gy while HCAEC needed 22.5 Gy for similar effects. The antiproliferative effect was dose dependent in all cell strains. The effect of irradiation with 22.5 Gy on smooth muscle alpha-actin, vimentin, and alpha-tubulin of HCPSMC and HCMSMC and on von Willebrand factor (vWF), vimentin, and alpha-tubulin of HCAEC was investigated by means of indirect immunofluorescence. Within 18 h after irradiation no effect on cytoskeletal components and vWF was documented. This in vitro study demonstrates that irradiation inhibits HCMSMC and HCPSMC at lower dose rates compared to HCAEC.
Atherosclerosis 2000 Sep
PMID:Different radiosensitivity of smooth muscle cells and endothelial cells in vitro as demonstrated by irradiation from a Re-188 filled balloon catheter. 1099 37

The aim of this study is to determine whether subpopulations of smooth muscle cells (SMC), as distinguished by variations in contractile and cytoskeletal proteins, appear in the neointima at different times after vascular injury, and/or whether subpopulations develop during serial passaging of these cells. Rat aortae and rabbit carotid arteries were injured with a 2F Fogarty balloon catheter and cultures established from the resulting neointima and the media 2, 6, 12, 16 and 24 weeks later. Cultures were examined at passages 1-5 and subpopulations of SMC categorised by intensity of staining for each protein by immunohistochemistry. Two populations of SMC with different staining intensities ('++', '+') were observed for each of the following proteins: alpha-SM actin, SM-myosin, desmin and vimentin. Populations without these proteins were also found. Changes in the percentages of cells expressing these proteins were transitory, indicating that the populations were not limited to a particular tissue (neointima or media), time after injury or passage number. One exception was found in rabbit cultures where the number of desmin-expressing cells quickly decreased with both time after injury and time in culture. Subpopulations of SMC were found at all times after injury in the media and neointima of rat and rabbit arteries, and after multiple passage of these cells. There was no pattern of development of one population suggesting that either no subpopulation has a proliferative or migratory advantage over others, or that only one population exists that is capable of diverse phenotypic changes.
Atherosclerosis 2001 Feb 01
PMID:Smooth muscle cells of injured rat and rabbit arteries in culture: contractile and cytoskeletal proteins. 1116 61

Although intimal hyperplasia is a major cause limiting the long-term patency of the vein grafts, its precise mechanisms, including the effect of poor runoff, has not yet been well characterized. We thus designed the present study to try to determine the effect of poor runoff arterial flow to the phenotypic alterations of the graft wall by immnohistochemistry using anti-intermediate filaments (alpha-SM actin, desmin, and vimentin) and anti-myosin heavy chain (SM1, SM2, and SMemb) specific antibodies. Vein grafts implanted under the poor runoff hind limb of rabbits showed enhanced intimal hyperplasia, however, no apparent difference in the cytoskeleton expression, including intermediate filaments and MHC, between two groups until 4 weeks. Interestingly, six of eight vein grafts at 2 weeks after implantation in both groups showed the accumulations of perivascular fibroblast-like phenotype (negative for SM1, alpha-SM actin, and desmin) in some parts of the outer neointima, whereas the inner neointima at 2 weeks and the whole neointima at 4 weeks were mainly occupied by a smooth muscle phenotype (positive for these three). Although the cellular origin of these cells is still unknown, these results suggest that the migration of non-muscle mesenchymal cells is involved in the neointima and thus may provide a clue for better understanding vein graft remodeling.
Atherosclerosis 2001 Feb 01
PMID:Immunohistochemical phenotypic alterations of rabbit autologous vein grafts implanted under arterial circulation with or without poor distal runoff-implications of vein graft remodeling. 1116 67

Macrophage apoptosis contributes to the development of human atherosclerotic lesions. Oxidised LDL may be involved in macrophage death in vivo. We examined morphological and biochemical changes to the vimentin filament network during apoptosis of human macrophages. Only oxidised LDL, but not native or acetylated LDL, induced apoptosis, wherein vimentin was cleaved into fragments of 48-50, 46, 29 and 26 kDa. The use of caspase inhibitors suggested that caspase-6 mediates the formation of the 26 and 46 kDa fragments of vimentin. We were unable to demonstrate any significant involvement of caspase-3 in vimentin cleavage. However, caspase-3 was clearly activated during apoptosis whilst caspase-6 expression in macrophages was minimal. Vimentin filament breakdown occurred early during apoptosis and vimentin immunoreactivity was present in apoptotic bodies. However, the application of caspase inhibitors had no effect on the morphology of the vimentin network in apoptotic cells, suggesting that filament breakdown is not mediated by caspase proteolysis. Similar changes in vimentin were also seen in gliotoxin-induced apoptosis.
Atherosclerosis 2001 May
PMID:Changes in vimentin in human macrophages during apoptosis induced by oxidised low density lipoprotein. 1136 6

Long-term patency of human saphenous vein bypass grafts is low because of intimal thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to be essential for the VSMC migration that contributes to intimal thickening. We examined VSMC phenotype and MMP activity in saphenous veins obtained before and after surgical manipulation. Surgical preparation of the veins significantly increased pro-MMP-1 expression by 2-fold and significantly reduced tissue inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected. Furthermore, caseinolytic and gelatinolytic activities measured by in situ zymography were dramatically elevated by injury. The expression of desmin and smoothelin was significantly decreased by injury, whereas vimentin expression was significantly increased. In addition, these changes in phenotype and MMP activity were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our data show that surgical preparative injury induces phenotypic modulation of a subpopulation of medial VSMCs to a synthetic phenotype and increases MMP activity. This may favor matrix degradation, VSMC migration, and the subsequent intimal thickening that leads to graft failure.
 ...
PMID:Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein. 1145 43

The endothelium is a single layer of cells lining the inside face of all blood vessels. It constitutes a major metabolic organ which is critically involved in the generation and the regulation of multiple physiological and pathological processes such as coagulation, hemostasis, inflammation, atherosclerosis, angiogenesis and cancerous metastasis dissemination. In order to increase our knowledge about the protein content and the main biological pathways of human vascular endothelial cells, we have undertaken the proteomic analysis of the most explored present endothelial cell model, i.e. primocultures of human umbilical vein endothelial cells (HUVECs). Using low levels of protein loads (~ 30 nug), the association of two-dimensional electrophoresis with matrix-assisted laser desorption/ionization-time of flight mass spectrometry, liquid chromatography-tandem mass spectrometry and database interrogations allowed us to identify 53 proteins of suspected endothelial origin in quiescent HUVECs. Beside cytoskeletal proteins such as actin, tubulin, tropomyosin and vimentin, we identified various proteins more especially implicated in cellular motility and plasticity (e.g. cofilin, F-actin capping protein and prefoldin), in regulation of apoptosis and senescence (protease inhibitor 9, glucose related proteins, heat shock proteins, thioredoxin peroxidase, nucleophosmin) as well as other proteins implicated in coagulation (annexin V, high mobility group protein), antigen presentation (valosin containing protein and ubiquitin carboxyl terminal hydrolase isozyme L1) and enzymatic capabilities (glutathione-S-transferase, protein disulfide isomerases, lactate deshydrogenase). The presented annotated 2-D maps of HUVECs will be soon available on the web at http://www. huvec.com.
 ...
PMID:Proteomic study of human umbilical vein endothelial cells in culture. 1274 50


<< Previous 1 2 3 4 5 6 Next >>