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Smoothelin

About: Smoothelin is a research topic. Over the lifetime, 264 publications have been published within this topic receiving 14069 citations.


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TL;DR: In this article, the authors examined human carotid endarterectomy specimens for the presence of fibrocytes by immunohistochemistry staining for CD34/procollagen I and leukocyte specific protein-1/pro-collagen-I. They found that the cells possessed a smooth muscle-like spindle shape, produced collagen, and consistent with being SM-like cells they co-localized with transformation growth factor beta, but not serum amyloid P factors, known to promote and inhibit their formation.
Abstract: Aim The stability of an atherosclerotic plaque is a key-determining factor in the clinical outcome of cardiovascular disease. In this respect, smooth muscle (SM) alfa actin positive cells play an important role in maintaining plaque stability through formation of a fibrous cap. Recent evidence suggests that circulating progenitors may be a source of these cells. We hypothesized that they may be fibrocytes bone-marrow derived cells that acquire SM-like characteristics, including the expression of SM alfa actin. Methods We examined human carotid endarterectomy specimens for the presence of fibrocytes by immunohistochemistry staining for CD34/procollagen I and leukocyte specific protein-1/procollagen I) and examined fibrocyte differentiation in vitro. Results Fibrocytes were found in regions of plaque growth/healing. They possessed a SM-like spindle shape, produced collagen, and consistent with being fibrocytes they co-localized with transformation growth factor beta, but not serum amyloid P factors, known to promote and inhibit their formation, respectively. While fibrocytes were detected in regions of new growth in 35/40 specimens, only 1/3 of the specimens expressed the SM cell marker calponin, and smoothelin was absent, in these regions. Conclusion Our results demonstrate that fibrocytes contribute to formation of the fibrous cap. With fibrocytes being a monocyte derived cell, we suggest that monocytes may play a more crucial role in the clinical outcome of atherosclerosis than previously realized as they not only contribute directly to plaque instability (through foam cell formation), but also promote plaque stability by transformation into a fibrocyte.

63 citations

Journal ArticleDOI
TL;DR: This work aimed to elucidate the clinicopathological and immunohistochemical features of leiomyosarcoma of the gastrointestinal (GI) tract.
Abstract: Aims We aimed to elucidate the clinicopathological and immunohistochemical features of leiomyosarcoma (LMS) of the gastrointestinal (GI) tract. Methods and results We encountered seven cases of GI-LMS in the colon (n = 4), rectum (n = 1), jejunum (n = 1) and stomach (n = 1). They ranged from 1 to 25 cm (median, 8.5 cm) in size and had high mitotic counts (median 38 per 50 high-power fields). Morphologically, the tumours were composed mainly of spindle cells with eosinophilic cytoplasm and various degrees of nuclear atypia and pleomorphism. Immunohistochemically, the tumours were positive for α-smooth muscle actin (86%), muscle-specific actin (71%), desmin (86%), calponin (71%), h-caldesmon (57%) and smoothelin (71%). All were negative for KIT, CD34, protein kinase C theta and DOG1. Local recurrence and distant metastasis occurred in one and three patients, respectively. We then reviewed 55 cases of GI-LMS from the era following the recognition of gastrointestinal stromal tumours. Among 29 of 55 cases for whom follow-up information was available, the estimated 5-year overall survival rate was 51.6%; tumour size ≥5 cm was correlated significantly with shorter overall survival time (P = 0.0016), while mitotic count (≥50 or ≥100 per 50 high-power fields) proved to be no prognostic factor. Conclusions GI-LMSs have distinctive clinicopathological and immunohistochemical features and exhibit aggressive biological behaviour.

62 citations

Journal ArticleDOI
TL;DR: It is shown that the frequencies of major (frequency >0.1 in a population) haplotypes can be inferred rather accurately from the pooled DNA data by the maximum-likelihood method, although with some limitations.
Abstract: Inference of haplotypes is important for many genetic approaches, including the process of assigning a phenotype to a genetic region. Usually, the population frequencies of haplotypes, as well as the diplotype configuration of each subject, are estimated from a set of genotypes of the subjects in a sample from the population. We have developed an algorithm to infer haplotype frequencies and the combination of haplotype copies in each pool by using pooled DNA data. The input data are the genotypes in pooled DNA samples, each of which contains the quantitative genotype data from one to six subjects. The algorithm infers by the maximum-likelihood method both frequencies of the haplotypes in the population and the combination of haplotype copies in each pool by an expectation-maximization algorithm. The algorithm was implemented in the computer program LDPooled. We also used the bootstrap method to calculate the standard errors of the estimated haplotype frequencies. Using this program, we analyzed the published genotype data for the SAA (n=156), MTHFR (n=80), and NAT2 (n=116) genes, as well as the smoothelin gene (n=102). Our study has shown that the frequencies of major (frequency >0.1 in a population) haplotypes can be inferred rather accurately from the pooled DNA data by the maximum-likelihood method, although with some limitations. The estimated D and D′ values had large variations except when |D| values were >0.1. The estimated linkage-disequilibrium measure ρ2 for 36 linked loci of the smoothelin gene when one- and two-subject pool protocols were used suggested that the gross pattern of the distribution of the measure can be reproduced using the two-subject pool data.

62 citations

Journal ArticleDOI
TL;DR: It is demonstrated for the first time that the TxA2 mimetic U46619 induces differentiation of human adipose tissue‐derived MSCs (hADSCs) to smooth muscle‐like cells, as demonstrated by increased expression of Smooth muscle‐specific contractile proteins such as α‐smooth muscle actin (α‐SMA).
Abstract: Thromboxane A(2) (TxA(2)) is involved in smooth muscle contraction and atherosclerotic vascular diseases. Accumulating evidence suggests a pivotal role for mesenchymal stem cells (MSCs) in vascular remodeling. In the present study, we demonstrate for the first time that the TxA(2) mimetic U46619 induces differentiation of human adipose tissue-derived MSCs (hADSCs) to smooth muscle-like cells, as demonstrated by increased expression of smooth muscle-specific contractile proteins such as alpha-smooth muscle actin (alpha-SMA), calponin, smoothelin, and smooth muscle-myosin heavy chain. Using an in vitro collagen gel lattice contraction assay, we showed that U46619-induced expression of the contractile proteins was associated with increased contractility of the cells. U46619 increased the intracellular Ca(2+) concentration in hADSCs and pretreatment of the cells with the thromboxane receptor antagonist SQ29548 or the calmodulin (CaM) inhibitor W13 abrogated the U46619-induced alpha-SMA expression and contractility, suggesting a pivotal role of Ca(2+)/CaM in the U46619-stimulated smooth muscle differentiation of hADSCs. In addition, U46619 elicited activation of RhoA in hADSCs, and pretreatment of the cells with the Rho kinase-specific inhibitor Y27632 or overexpression of the dominant-negative mutants of RhoA and Rho kinase blocked U46619-stimulated alpha-SMA expression and contractility. Furthermore, U46619 induced phosphorylation of myosin light chain (MLC) through CaM/MLC kinase- and Rho kinase-dependent pathways, and the MLC kinase inhibitor ML-7 abrogated U46619-induced alpha-SMA expression and contractility. These results suggest that U46619 induces differentiation of hADSCs to contractile smooth muscle-like cells through CaM/MLCK- and RhoA-Rho kinase-dependent actin polymerization.

61 citations

Journal ArticleDOI
TL;DR: Vessels with various stages of VSMC differentiation in AVMs and CCMs are described and the subendothelial layer of CCMs commonly expresses &agr;-SMA and less commonly expresses myosin heavy chain.
Abstract: OBJECTIVE The pathogenesis of central nervous system vascular malformations likely involves the abnormal assembly, differentiation of vascular smooth muscle cells (VSMC), or both in association with dysmorphic vessel wall. We hypothesize that intracranial arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) exhibit distinct patterns of expression of molecular markers of differentiation and maturity of VSMCs. We further speculate that the unique VSMC phenotype in the different lesions is not necessarily maintained in cell culture. METHODS Paraffin-embedded sections of five AVMs, CCMs, and control brain tissues were stained immunohistochemically with antibodies to alpha-smooth muscle actin (alpha-SMA), myosin heavy chain, and smoothelin, a novel marker for contractile VSMC phenotype. Large (> or =100 microm) and small (<100 microm) vessels were counted and assessed for immunoexpression of each protein, then categorized according to expression of one or more of these markers. Cultured nonendothelial cells isolated from four other excised AVM and CCM lesions were assessed for immunoexpression of the same antibodies. RESULTS Alpha-SMA was universally expressed in all vessels in AVMs and in control brains. It was expressed in the subendothelial layer of 97% of large caverns and 85% of small caverns and in scattered intercavernous connective tissue fibrocytes in CCMs. Myosin heavy chain was expressed in the majority of brain and AVM vessels, except for normal veins, and in the subendothelial layer of more than half of the caverns in CCMs. Smoothelin expression was less prevalent in large vessels in AVMs than in control brains and was not found in any caverns in CCMs (large vessels in control brains, 40.9%; AVMs, 21.9%; CCMs, 0%; P < 0.0001). Cultured AVM and CCM nonendothelial cells expressed alpha-SMA, but myosin heavy chain was expressed weakly in cells from only one CCM. Smoothelin was negative in all cells. CONCLUSION We describe vessels with various stages of VSMC differentiation in AVMs and CCMs. The subendothelial layer of CCMs commonly expresses alpha-SMA and less commonly expresses myosin heavy chain. Expression of smoothelin was less prevalent in large AVM vessels than in normal brain, which may reflect the loss of contractile property associated with hemodynamic stress. It is difficult to evaluate VSMC differentiation in culture because of phenotypic change.

59 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202113
202012
20196
20188
201713
20165