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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smooth muscle cell (SMC) proliferation is a poorly understood process that plays a critical role in several pathological states, including atherosclerosis and hypertension. Recent work suggests that the oncogene c-myb and myosin, a ubiquitous cytoskeletal protein, may be directly involved in this process. We have used antisense nonmuscle myosin heavy chain (NMMHC) or c-myb phosphorothiolate oligonucleotides to inhibit proliferation of SMCs in vitro. The suppression of growth is accompanied by reductions in the concentrations of NMMHC and c-myb mRNAs as well as decreases in the levels of the corresponding proteins. The specificity of the antiproliferative effect is underscored by the absence of any detectable growth inhibition with sense NMMHC or c-myb phosphorothiolate oligonucleotides, an antisense c-myb mismatch phosphorothiolate oligonucleotide, or an antisense thrombomodulin phosphorothiolate oligonucleotide. Furthermore, the treatment of SMCs with antisense phosphorothiolate oligonucleotides for as little as 2 hours causes maximal inhibition of cell growth over the next 72 hours. Under these conditions, SMCs attain normal rates of growth over the following 48 hours, which shows that proliferation is suppressed in a reversible fashion by antisense phosphorothiolate oligonucleotides. These experiments indicate that both c-myb and nonmuscle myosin play critical roles in SMC proliferation and that reductions of either mRNA by antisense phosphorothiolate oligonucleotides arrest the process.
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PMID:Antisense nonmuscle myosin heavy chain and c-myb oligonucleotides suppress smooth muscle cell proliferation in vitro. 155 Dec 7

Two monoclonal antimyosin antibodies, Western blotting experiments, and immunofluorescence procedures were used to investigate myosin isoform expression in normal and atherosclerotic aortas of adult rabbits. The SM-E7 antibody reacted with the two myosin heavy chain (MHC) isoforms of smooth muscle (SM) type (SM-MHC-1 and SM-MHC-2) expressed in the adult rabbit aorta. The NM-G2 antibody recognized an epitope shared by the nonmuscle (NM) myosin heavy chains (NM-MHC) present in fibroblasts, macrophages, lymphocytes, and platelets. Two smooth muscle cell (SMC) populations were identified in the medial layer of normal adult aorta, namely cells that contained SM myosin exclusively and cells that showed the coexistence of SM and NM myosin isoforms. The size of the cell population with double myosin isoform content increased markedly during experimental atherogenesis and represented by far the predominant SMC phenotype in the atherosclerotic plaque. Western blotting analysis performed on crude extracts from the atherosclerotic plaque showed the presence of SM-MHC-1 and NM-MHC isoforms in this tissue. Co-expression of SM and NM myosin at the molecular and the cellular level were found in aortic tissue during the early stages of development. These results indicate that in experimental atherosclerosis, the accumulation in the plaque of SMC with an "immature" pattern of myosin isoform expression is accompanied by similar modifications in the differentiation pattern of SMC of the underlying media.
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PMID:Myosin isoform expression and smooth muscle cell heterogeneity in normal and atherosclerotic rabbit aorta. 170 Aug 96

Adult rabbit smooth muscles contain two types of myosin heavy chain (MHC) isoforms, SM1 and SM2 which are generated through alternative RNA splicing from a single gene (Nagai, R., Kuro-o, M., Babij, P. & Periasamy, M. (1989) J. Biol. Chem. 264, 9734-9737). We previously reported that the expression of SM1 and SM2 during vascular development is differentially regulated at the level of RNA splicing, whereby SM1 is constitutively expressed from early development but SM2 appear after birth (Kuro-o, M., Nagai, R., Tsuchimochi, H., Katoh, H., Yazaki, Y., Ohkubo, A. & Takaku, F. (1989) J. Biol. Chem. 264, 18272-18275). We also demonstrated that embryonic vascular smooth muscles contain a third type of MHC isoform, referred to as SMemb in this report, which comigrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with SM2. In the present study we have isolated and characterized a cDNA clone (FSMHC34) for SMemb. FSMHC34 encodes the light meromyosin region including the carboxyl terminus and showed 70% amino acid sequence identity with SM1 or SM2. SMemb is a nonmuscle-type MHC and identical with brain MHC, but clearly distinct from 196-kDa nonmuscle MHC in cultured smooth muscle cells. The expression of SMemb was predominant in embryonic and perinatal aortas, but down-regulated with vascular development. Interestingly SMemb was reexpressed in proliferating smooth muscle cells of arteriosclerotic neointimas. These results suggest that smooth muscle proliferation is coupled to the expression of SMemb and that dedifferentiation of smooth muscles toward the embryonic phenotype is involved in the mechanisms underlying atherosclerosis.
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PMID:cDNA cloning of a myosin heavy chain isoform in embryonic smooth muscle and its expression during vascular development and in arteriosclerosis. 199 31

Vascular smooth muscle cells (VSMC) are the principal cellular component of the blood vessel wall. Atherosclerosis, hypertension, and angiogenesis are associated with abnormal VSMC growth. Angiotensin II is hypertrophic for cultured adult rat aortic VSMC, whereas platelet-derived growth factor and serum are hyperplastic. To identify changes in specific proteins associated with either hyperplastic or hypertrophic growth, high resolution two-dimensional gel electrophoresis was performed on extracts from quiescent rat aortic VSMC and from VSMC exposed for 24 h to growth factors (10% fetal calf serum, platelet-derived growth factor, or angiotensin II). 12 proteins were up-regulated and 5 down-regulated by treatment with growth factors. Eight of the up-regulated and one of the down-regulated proteins were identified by internal protein microsequencing from electroblotted two-dimensional gels or by co-electrophoresis of purified proteins in two-dimensional gels. Four of the proteins up-regulated by growth factors were identified as mediators of protein folding. These were heat shock proteins, HSP-60 and HSP-70, protein disulfide isomerase, and protein disulfide isomerase isozyme Q-2. Additional proteins were identified as elongation factor EF-1 beta, a component of the protein synthesis apparatus, and calreticulin, another putative molecular chaperone. Vimentin and actin were also up-regulated, whereas an isoform of myosin heavy chain was down-regulated. Hyperplastic and hypertrophic growth were accompanied by similar changes in protein expression, suggesting that both types of growth require up-regulation of the protein synthesis and folding machinery.
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PMID:Components of the protein synthesis and folding machinery are induced in vascular smooth muscle cells by hypertrophic and hyperplastic agents. Identification by comparative protein phenotyping and microsequencing. 767 76

Molecular biology has given a strong impact on cardiovascular medicine, not only clinical but also laboratory medicine. cDNA cloning and analysis of gene structures encoding functional proteins or peptides in the cardiovascular system provided insight into molecular mechanisms underlying heart diseases or atherosclerosis. Nucleotide or amino acid sequences for these molecules are useful information for manufacturing bioactive peptides or developing immunoassays. These cDNA clones or genes are useful molecular tools diagnosing patients with high risks for cardiovascular diseases. Recent advances in this field have been made in identification of point mutations of many genes important for cardiovascular functions, including LDL receptors in familial hyperlipidemia, cardiac myosin heavy chain genes in familial hypertrophic cardiomyopathy, mitochondrial DNA in mitochondria cardiomyopathy, or dystrophin genes in secondary cardiomyopathy. Molecular probes are further used in detection of microorganisms causing myocarditis. These progresses that have been made in laboratories of basic researchers will be introduced into clinical medicine and expand the field the laboratory medicine is involved.
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PMID:[Molecular biology in cardiovascular medicine]. 773 12

Smooth muscle is an important component of the vessel wall. Smooth muscle cell undergoes phenotypic modulation during development of vascular lesions, such as atherosclerosis and restenosis following percutaneous transluminal coronary angioplasty (PTCA). In order to understand the mechanism of vascular remodeling, it is important to identify the smooth muscle cell in the vascular lesion and identify its phenotype by using molecular markers specific to the smooth muscle cell. Three types of myosin heavy chain (MHC) isoforms (SM1, SM2 and SMemb) expressed in smooth muscles are suitable for this purpose. In this study we first demonstrated that the expression of smooth muscle specific MHCs, such as SM1 and SM2, is reduced in human coronary arteries after the fifth decade. On the other hand, rapidly proliferating smooth muscles in the restenotic lesion express abundant SMemb but less amount of SM2. These observations indicate that deranged vascular smooth muscle differentiation is involved the development of vascular lesion. We furthermore demonstrated that smooth muscle-specific MHC is released into serum from the arterial wall following vascular damage as in dissecting aneurysm. Circulating smooth muscle MHC level was elevated 5-10 times above normal at 24 hours after aortic dissection as determined using a sensitive ELISA. We conclude from these results that smooth muscle MHC isoforms are important molecular markers for vascular pathology as well as for biochemical diagnosis of vascular injuries.
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PMID:[Smooth muscle myosin heavy chain expression in the arterial wall; a new viewpoint for vascular pathology]. 773 13

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

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

Intimal accumulation of macrophages and changes in the phenotype and growth properties of vascular smooth muscle cells (SMCs) represent key events in the development of atherosclerotic lesions. Here we report on the in vivo effect exerted by nitrendipine on aortic tissue of cholesterol-fed rabbits. We have focused especially on the myosin heavy chain (MyHC) pattern expressed by aortic SMC, taken as a marker of cell differentiation. Using monoclonal antibodies specific to the different forms of MyHC, three differentiation steps were determined: adult, postnatal, and fetal. Nitrendipine administered in conjunction with a cholesterol-enriched diet reduced the development of atherosclerotic lesions (atherosclerosis index: 0.21 vs. 0.32 in untreated animals, p< 0.005), despite persistently high serum cholesterol levels. Compared to untreated controls, nitrendipine-treated animals displayed a decreased number of postnatal-type SMCs in the media underlying the plaque (prevalence index: 0.07 vs. 0.26, p < 0.0001 and a lower aortic cholesterol content (free cholesterol: 3.3 vs. 11.5 ng/mg, p< 0.0001; esterified cholesterol: 7.2 vs. 40.5 ng/mg, p< 0.0001). Moreover, nitrendipine treatment decreased the intimal accumulation of macrophages and fetal-type SMCs. It is conceivable that calcium antagonists may exert their antiatherogenic effect, at least in part, through cellular changes unrelated to the classical risk factors.
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PMID:Antiatherogenic action of nitrendipine in hypercholesterolemic rabbits: changes in aortic macrophage accumulation and smooth muscle cell phenotype. 860 27

Phenotypic change of the smooth muscle cell (SMC) is implicated in normal development as well as several pathological processes including atherosclerosis. In general, differentiation SMCs show contractile responses to different exogenous stimuli and are inactive in mitosis, while undifferentiated or dedifferentiated SMCs show a mitogenic response and are not contractible. In the present review, we describe structural and functional aspects of the phenotypic change of SMCs with special reference to their role in atherogenesis. SMCs derived from atherosclerotic intimal lesions (intimal SMCs) show more amplified growth potential and chemotactic activity than medial SMCs; and furthermore, they require a macrophage-like phenotype: uptake of modified low density lipoproteins through the scavenger receptor, which leads to high tendency toward foam cell formation. Platelet-derived growth factor, secreted from most of the cells existing in atherosclerotic plaques, is one of candidates that promote the formation of such a highly dedifferentiated intimal SMC. Clinical and experimental evidence supports the concept that an appearance of the pathological intimal SMCs is a key step for their abnormal proliferation in atheromatous lesions. Recent advances in characterization of the phenotype-specific molecular markers for SMC, such as myosin heavy chain, caldesmon, and calponin, are also described.
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PMID:[Phenotypic change of the smooth muscle cell and atherosclerosis]. 872 89


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