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)

Although vascular smooth muscle cells (SMCs) play a key role in the development of atherosclerotic lesions, they are not a homogeneous cell type. Myosin has been used as a marker of SMC differentiation in order to identify distinct SMC populations in the adult rabbit aorta. The medial layer of the normal adult aorta contains predominantly 'adult' type SMCs, which express smooth muscle (SM) myosin isoforms exclusively, and a minority of 'immature' type SMCs, which coexpress SM and nonmuscle (NM) myosin isoforms. The size of this latter SMC subpopulation, showing the 'immature' pattern of myosin isoform expression, increases markedly in the aortic media during experimental atherogenesis, and represents a major SMC type in the atherosclerotic plaque. The dihydropyridine derivative, nifedipine, has a marked effect on NM myosin expression and SMC differentiation in vitro. In vivo, short term administration of nifedipine resulted in the disappearance of 'immature' type SMCs from the aortic media of both normocholesterolaemic and hypercholesterolaemic adult rabbits. Moreover, in a model of atherosclerosis prevention, nifedipine significantly reduced the area of aortic intimal thickening and reduced the size of the 'immature' type SMC population both in the aortic media and intima of the hypercholesterolaemic rabbit.
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PMID:Impact of nifedipine on vascular smooth muscle cell differentiation. Implications for atherogenesis. 753

Smooth muscle myosin heavy chains (MHCs) exist in multiple isoforms. Rabbit smooth muscles contain at least three types of MHC isoforms: SM1 (204 kD), SM2 (200 kD), and SMemb (200 kD). SM1 and SM2 are specific to smooth muscles, but SMemb is a nonmuscle-type MHC abundantly expressed in the embryonic aorta. We recently reported that these three MHC isoforms are differentially expressed in rabbit during normal vascular development and in experimental arteriosclerosis and atherosclerosis. The purpose of this study was to clarify whether expression of human smooth muscle MHC isoforms is regulated in developing arteries and in atherosclerotic lesions. To accomplish this, we have isolated and characterized three cDNA clones from human smooth muscle: SMHC94 (SM1), SMHC93 (SM2), and HSME6 (SMemb). The expression of SM2 mRNA in the fetal aorta was significantly lower as compared with SM1 mRNA, but the ratio of SM2 to SM1 mRNA was increased after birth. SMemb mRNA in the aorta was decreased after birth but appeared to be increased in the aged. To further examine the MHC expression at the histological level, we have developed three antibodies against human SM1, SM2, and SMemb using the isoform-specific sequences of the carboxyl terminal end. Immunohistologically, SM1 was constitutively positive from the fetal stage to adulthood in the apparently normal media of the aorta and coronary arteries, whereas SM2 was negative in fetal arteries of the early gestational stage. In human, unlike rabbit, aorta or coronary arteries, SMemb was detected even in the adult. However, smaller-sized arteries, like the vasa vasorum of the aorta or intramyocardial coronary arterioles, were negative for SMemb. Diffuse intimal thickening in the major coronary arteries was found to be composed of smooth muscles, reacting equally to three antibodies for MHC isoforms, but reactivities with anti-SM2 antibody were reduced with aging. With progression of atherosclerosis, intimal smooth muscles diminished the expression of not only SM2 but also SM1, whereas alpha-smooth muscle actin was well preserved. We conclude from these results that smooth muscle MHC isoforms are important molecular markers for studying human vascular smooth muscle cell differentiation as well as the cellular mechanisms of atherosclerosis.
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PMID:Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis. 791 68

Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years. Pathological studies show left ventricular hypertrophy and fibrosis with varying degrees of small vessel disease, the functional significance of which is uncertain. Hypertension was recognized as an important cofactor in the development of fatal congestive heart failure in diabetics. On cardiac catheterization, in patients symptomatic of heart failure, either congestive or restrictive patterns have been observed. In contrast, asymptomatic diabetics had decreased left ventricular compliance but normal systolic function on hemodynamic study. Noninvasive studies show alterations in systolic and especially diastolic function, particularly in diabetics with microvascular complications and/or coexistent hypertension. Using load-independent measures of contractility, however, systolic function was generally found to be normal in asymptomatic normotensive diabetics. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. Decreased left ventricular compliance and increased interstitial connective tissue were observed in chronically diabetic dogs. In contrast, ventricular myocardium from diabetic rats exhibits a reversible decrease in the speed of contraction, prolongation of contraction, and a delay in relaxation. These mechanical changes are associated with a decreased myosin ATPase, a shift in myosin isoenzyme distribution, alterations in a variety of Ca2+ fluxes, and changes in responses to alpha- and beta-adrenergic and cholinergic stimulation. These biochemical changes may be secondary to alterations in carbohydrate, lipid, and adenine nucleotide metabolism in the diabetic heart.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetic cardiomyopathy. 808 30

To elucidate the mechanism of the development of atherosclerosis, we have investigated the cell population of phenotypes of contractile (C-SMC) and synthetic (S-SMC) states of SMCs at proximal and distal areas of bifurcation of the celiac and superior mesenteric arteries in children and young persons by transmission electron microscopy. The previous studies in patients with hypercholesterolemia and who were young indicated that percentages of proximal area at bifurcation of both arteries were greater than that of C-SMC (P 0.01), and that C-SMCs at distal area were less than that of S-SMC (P 0.05). Ultrastructurally, SMCs at proximal area were S-SMCs containing many synthetic organelles and intermediate filaments. On the other hand, those at distal area were C-SMCs containing actin, myosin, dense bodies and microtubules. In the present study, we have ascertained that the phenotypic modulation of SMCs in the intima and media might correlate to the physico-medial relationship between SMCs and elastic tissues. In this communication, we have observed that the intimal SMCs transformed their phenotypes from the internal elastic layer (S-SMC) to the superficial layer (C-SMC), and that the medial SMCs in the arteries of the young clearly consisted of two types: one type adhered to the elastic layer and the other type existed with the separated one. The difference between both areas in the relatively young need to be observed in detail from now on. In summary, the vascular SMCs and the elastic lamina are considered to contribute to the subsequent phenotypic modulation and their migration of SMCs.
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PMID:The role of vascular smooth muscle cell phenotypic modulation at the aortic branch in atherogenesis. 824 Oct 31

The severity and frequency of atherosclerosis, diabetes, and ischemic heart disease, which affect cardiac function, increase with aging. Although there are many reports about hemodynamic and histopathological studies about aging hearts, there are very few studies on changes in structural proteins in aging hearts. We investigated the contractile proteins of the left ventricles in rats aged 6, 12 and 125 weeks using two-dimensional electrophoresis. There were no difference in structural proteins in heart between 6-week and 12-week-old rats. The contents of myosin heavy chain, myosin light chain 2, actin, troponin-I in 125-week-old rats decreased compared with those of 12-week-old rats. Myosin heavy chain, which is one component of myosin, interacts with actin and changes chemical energy to mechanical energy. Therefore its decrease leads to a decline in myocardial contractility. These results seem to indicate one of the most important changes in the aging rat heart, as well as impairment in relaxation by the increase of interstitial fibrosis and decline of Ca uptake by sarcoplasmic reticulum.
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PMID:[Analysis by two-dimensional electrophoresis of the cause of myocardial dysfunction in aging rat hearts]. 836 Oct 80

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

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

Actually more than 80% of heart recipients survive the first postoperative year. Early death is mainly caused by rejection and acute infection. After the first year progressive graft atherosclerosis has the greatest impact on prognosis. The review presents scintigraphic methods that have reached clinical impact in the diagnosis of rejection and vascular complications. Immunoscintigraphy with 111In-labelled monoclonal antibodies against myosin proved to be of importance in the diagnosis of rejection especially in long-term follow-up. Perfusion scintigraphy reveals vital and ischemic myocardium. In heart transplant recipients radionuclide ventriculography has been widely replaced by echocardiography. Up to now, the evaluation of increasing nerval integration with 123I-MIBG has not reached clinical impact.
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PMID:[Conventional nuclear medical diagnosis in the after care of heart transplantation]. 874 70

To investigate the mechanisms for intracellular signaling and increased vascular tone by 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha), we measured mitogen-activated protein kinase (MAPK) activity and myosin regulatory light chain (LC20) phosphorylation in porcine carotid arteries incubated with 8-epi-PGF2 alpha or PGF2 alpha. With stimulation by either 8-epi-PGF2 alpha or PGF2 alpha. MAPK activity and the force of contraction rose in parallel and were maintained during the time of exposure to agonist (2 hours). LC20 phosphorylation levels rose and then partially declined during stimulation with either agonist. The effects of 8-epi-PGF2 alpha on contraction, MAPK activity, and myosin light chain phosphorylation were completely inhibited by the receptor antagonists, SQ-29548 and BMS-180291; the effects of PGF2 alpha were only partially inhibited by these compounds. Thus, intracellular signaling by 8-epi-PGF2 alpha in fully differentiated vascular smooth muscle, resulting in MAPK activation and increased myosin phosphorylation, is specifically mediated by an activation of thromboxane A2/prostaglandin endoperoxide receptors. Lipid peroxidation and 8-epi-PGF2 alpha production, resulting from such vascular pathological processes as atherosclerosis, lead to an activation of two intracellular signaling pathways in smooth muscle: one pathway results in the activation of MAPK, while the other results in myosin light chain phosphorylation.
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PMID:Intracellular signaling by 8-epi-prostaglandin F2 alpha is mediated by thromboxane A2/prostaglandin endoperoxide receptors in porcine carotid arteries. 878 Jul 11

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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