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)

We have examined the intermediate filament (IF) protein content of vascular smooth muscle (SM) cells from several arteries and veins in rabbits and quantitated the changes which occur in SM cell expression of these proteins in response to cholesterol feeding. Cells from control rabbit arteries expressed 30% of their IF protein as desmin, while veins expressed 50% as desmin. During development of diet-induced atherosclerosis, morphological changes in arterial SM cells in the intima correlate with changes in IF expression. There is a significant increase in total IF protein content, vimentin increased differentially in thoracic aorta and desmin in pulmonary artery. In abdominal aorta both increase equally. Cholesterol feeding also resulted in changes in the expression of subspecies of desmin, vimentin, and actin in the thoracic arch. Although cholesterol feeding did not produce obvious morphological changes in the veins examined, venous SM IF protein expression was also altered. In the vena cava of cholesterol-fed rabbits there was an increase in vimentin expression without the parallel increase in desmin that occurred in the arterial system. These studies show that cholesterol feeding of rabbits induces measurable changes in the amounts of IF proteins in both arterial atherosclerotic lesions and venous SM cells.
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PMID:Intermediate filament heterogeneity in normal and hypercholesterolemic rabbit vascular smooth muscle cells. 394 65

Aortic intima-medias of normal and cholesterol-fed rabbits were studied with EM and cells were isolated by enzyme digestion. The composition of cytoskeletal and cytocontractile proteins was determined with SDS-PAGE and the primary growth and thymidine incorporation rates were assessed after seeding the cells into tissue culture flasks. Ultrastructurally, the SMCs in the thickened atherosclerotic intima differed from the contractile medial SMCs in containing lipid vacuoles, enlarged endoplasmic reticulum and a reduced number of myofilaments, thus showing characteristics of dedifferentiated SMCs. In SDS-PAGE, freshly isolated cells from the atherosclerotic intima-medias had a lower content of myosin and actin, and a higher proportion of vimentin and desmin than SMCs from normal aortas. Enzyme-isolated SMCs from normal aortas did not start to grow and incorporate radioactive thymidine until 5-6 days after seeding, whereas those from atherosclerotic aortas did so within 2 days. After a week in culture, SMCs from both sources resembled each other, and had decreased contents of myosin and actin, and increased concentrations of vimentin in comparison to freshly isolated normal SMCs. The present results indicate (a) that morphological dedifferentiation of SMCs in aortic lesions of cholesterol-fed rabbits is associated with an increased proportion of the proteins of the intermediate filaments and a decrease in those of the thin and thick myofilaments as determined with SDS-PAGE, and (b) that similar changes take place when normal SMCs are cultured in vitro. The results also suggest (c) that enzyme-isolated atherosclerotic SMCs proliferate in a primary culture without the lag period that normal SMCs apparently require for dedifferentiation.
Atherosclerosis 1984 Jul
PMID:Growth properties and composition of cytoskeletal and cytocontractile proteins in aortic cells isolated and cultured from normal and atherosclerotic rabbits. 646 13

Dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) are important features of atherosclerosis. The molecular mechanisms are largely unclear; however, protein kinase C (PKC) is a key enzyme in the intracellular signaling pathways that mediate this process. We studied the activity and immunoreactivity of PKC-alpha in primary cultures of VSMCs from rat aortas under different conditions of growth and differentiation. PKC-alpha was determined under the following conditions: (1) during the growth phase and after confluence of cultured (passages 1 through 3) VSMCs, (2) before and after induction of differentiation in VSMCs by retinoic acid, and (3) in primary cultures of VSMCs from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats during early passages. PKC activity was measured by in vitro substrate phosphorylation. PKC-alpha immunoreactivity was assessed by Western blot using specific polyclonal antibodies and by immunostaining with confocal microscopy. Cell proliferation was measured by direct count. The cell phenotype was characterized by immunostaining and Western blot for alpha-actin and desmin. PKC-alpha expression and PKC activity during VSMC growth showed a decrease during rapid growth and an increase in confluent cells. This pattern was associated with the respective changes in cell differentiation. Retinoic acid induced an increase in PKC-alpha expression together with a more differentiated phenotype. Subcultured, rapidly growing VSMCs from SHR showed a decreased PKC-alpha expression compared with cells from WKY rats. To establish cause and effect, we next microinjected either PKC-alpha or inactivated material directly into dedifferentiated cells. We found that cells injected with active PKC-alpha expressed increased amounts of actin compared with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation of vascular smooth muscle cells and the regulation of protein kinase C-alpha. 800 Dec 76

Histochemical (= HIS) methods (haematoxylin-eosin, luxol fast blue, chromotrope aniline blue) and various immunohistochemical (= IH) markers (myoglobin, desmin, fibrinogen, complement C5b-9) were applied in parallel to test the efficiency, specificity and sensitivity for the recognition of early ischemic myocardial damage. The whole series was subgrouped into cardiac deaths (N = 35) and controls (N = 13). Cardiac deaths were sub-divided into 3 groups: 1. infarction visible in gross examination (N = 15), 2. coronary thrombosis without infarction (N = 11), 3. stenosing coronary atherosclerosis without infarction (N = 9). The control group (group 4) consisted of unnatural deaths with presumed short agonal periods (N = 13). Group 1 cases usually exhibited extended coagulation necrosis of the diffuse type and the contraction type in combination (1 exception). Group 2 showed mainly a patchy type of coagulation necrosis and contained 1 cases where all methods failed to react and 3 more cases where only the HIS methods failed to react. Group 3 and 4 were associated with a disseminated type of single and/or grouped fibre necrosis. In addition, the average reaction strengths showed a decrease from group 1 to group 4 which was more pronounced in the HIS reactions compared with the IH reactions. One case in group 1 showing negative IH reactions cannot be explained. Positive IH reactions observed in a few cases in group 2 contrasting with negative HIS reactions would indicate a greater sensitivity of this methodology and this interpretation also applies to groups 3 and 4. From pathophysiological considerations, the positive cases in groups 3 and 4 can be well explained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The application of selected histochemical and immunohistochemical markers and procedures to the diagnosis of early myocardial damage. 811 91

In a search for early atherosclerotic lesions, we have investigated grossly normal areas of human thoracic aortas taken at autopsy from 40 trauma victims aged from 3 to 40 years. Two areas of aorta were compared: lesion predisposed to atherosclerosis (LP) area localized on the dorsal aspect of the vessel along the row of intercostal branching sites, and lesion resistant (LR) area located on the ventral aspect of the vessel. Accumulation of apolipoprotein B (apo B) was found in LP aortic area of each child older than 6 years. Similar retention of apo B in LR area appeared only in aortas of teenagers. The apo B staining increased with age in both areas tested but was usually of a greater extent in LP area than in LR area. Typical smooth muscle cells (SMCs) and a few monocytes/macrophages (Mn/Mph) were revealed in the intimal layer of all aortas examined. The number of Mn/Mph dramatically increased in LP areas of individuals over 17 years. Quantitative study of double stained sections has shown a 2- to 6-fold enhanced number of Mn/Mph in LP area compared with LR aortic area of 10 men over 21 years. Focal infiltration of Mn/Mph in aortas of young adults occurred without endothelial denudation. In addition, some intimal SMCs in LP area of 12 aortas out of 29 expressed desmin and contained well-developed endoplasmic reticulum, while such cells were seldom detected in LP area of the vessels. Thus, focal accumulation of apo B with subsequent Mn/Mph infiltration and SMC phenotypic modulation in LP aortic area of young adults may be causally involved in fatty streak and atherosclerotic plaque formation.
Atherosclerosis 1993 May
PMID:Monocyte/macrophage accumulation and smooth muscle cell phenotypes in early atherosclerotic lesions of human aorta. 835 56

Study of 45 renal allograft nephrectomy specimens revealed the presence of relatively uncommon arterial vascular lesions: atheromatosis (12 cases) and a double layer of smooth muscle in the intima (Double Media) (4 cases). Histopathologic features of atheromatosis showed the presence of large lipid-laden cells localized in the intimal layer of arteries. Diagnosis of acute vascular rejection (AVR) was made in 19 cases. Diagnosis of chronic vascular rejection (CVR) was found in 4 cases. 22 cases showed lesions of both AVR and CVR. In 12 cases there was infiltration of the intima and media wall by foam cells closely resembling an atheromatous lesion. Four cases of Double Media were found in allografts with survival varying from 51 to 344 days. The presence of either atheromatous or double media does not correlate statistically with immunosuppressive treatment, blood pressure or with the presence of hypertriglyceridemia and/or hypercholesterolemia. Immunohistochemical investigation of atheromatosis revealed total negativity of the foam cells with antisera to: actin, myosin, desmin and myoglobin. Variable reactivity was observed with antisera to vimentin. Myointimal cells of Double Media expressed slight positivity for actin and vimentin. The double media lesion seems to be the result of a reparative vascular process secondary to rejection changes. Atheromatosis seems to be closely correlated to episodes of acute rejection. Vascular lesions in grafts are harbinger of poor prognosis. Double media lesion and atheromatosis do not seem to have a more unfavourable prognostic significance on the evolution of the transplants.
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PMID:Atheromatosis and double media: uncommon vascular lesions of renal allografts. 836 81

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.
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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.
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PMID:Expression of cytoskeletal proteins and ATPase activity in bovine femoral artery and vein intima. 886 55

In this study we asked whether the well-known atherosclerosis resistance of rats might be reduced with aging. Two groups of young, adult and aged Wistar rats, one of which was kept on a standard, low-cholesterol (CT) diet, and the other one was fed a 2% CT diet for 2 months were enrolled. Potential modifications in the phenotypic profile of aortic smooth muscle (SM) were assessed by SDS-gel electrophoresis, Western blotting and immunofluorescence procedures using a panel of monoclonal antibodies to myosin isoforms, cytoskeletal and extracellular matrix proteins. With development and aging, the expression of 196-kD non-muscle-type myosin heavy-chain isoform (MyHC), the EIIIA fibronectin variant and keratins was downregulated, whereas that of the 204- and 200-kD SM-type MyHC isoforms, SM-type alpha-actin and desmin did not change. The levels of hypercholesterolemia achieved in this model did not substantially modify the distribution of the downregulated markers, except for the subendothelial grouping of immature SM cells in aged rats. Morphometric measurements indicated a slight increase of medial cross-sectional area accompanied by a decrease in total SM cell number, both with aging and with hypercholesterolemia. In no circumstance was the presence of atherosclerotic lesions histologically detectable. Bromo-deoxyuridine (BrdU) incorporation analysis revealed a marked age-dependent decline in DNA synthesis and the formation of binucleated cells in aged aortas. This pattern was not influenced by hypercholesterolemia, except in aged rats where BrdU-positive SM cells are almost doubled. Our data indicate that aging and hypercholesterolemia cannot affect the phenotypic stability of rat SM cells and confirm that the change from a fully differentiated to an immature state is a general prerequisite to allow the development of atherosclerotic lesions in mammalian species.
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PMID:Atherosclerosis resistance in rats correlates with lack of expansion of an immature smooth muscle cell population. 925 93


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